The short answer is: YES, you can, but be careful. Some  info below.

There are more and more far east providers of Aicar who offer the substance at fractions of huge worldwide chem manufacturers cost. Most of them has lower purity, check COA and HPLC results.

AICAR is a potent AMPK activator for research. Current price at Sigma-Aldrich for 98% purity Aicar is 300 USD for 25 milligrams!

AICAR ≥98% (HPLC), powder CAS no. 2627-69-2

5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside, Acadesine, N1-(β-D-Ribofuranosyl)-5-aminoimidazole-4-carboxamide

So, how can you buy approximately 1 gram for the same price? – you buy from a smaller, non-worldwide, not so high rated raw chemical supplier THROUGH US.

1000 mg Aicar for $299

There are many peptide and body building sites that sell Aicar in 100 mg doses at around $100. Our price is half of that – but we don’t dilute it into liquid, you get the raw powder – and you can start experimenting with it.

100 mg Aicar for 59 dollars ONLY 

Please note that 100 mg is barely enough for any research if done on mammals. It can be used as a sample or test project on cell cultures. The smallest recommended amount you can test mammals with is 1 gram.


The Australian polidocanol (aethoxysklerol) study. Results at 2 years


Department of Surgery, Nepean Hospital, Sydney, Australia.



An ongoing study of the safety and effectiveness of polidocanol by 98 investigators in Australia infecting 16,804 limbs over 2 years.


To evaluate the complications of polidocanol and compare its effectiveness and complications with sodium tetradecyl sulphate (STD) and hypertonic saline.


A single-arm prospective study of polidocanol complications and its effectiveness as a sclerosant was performed. This was compared with each investigator’s previous experience with other sclerosing agents. Patients had either varicose veins or venule ectasias and/or spider veins (telangiectasia). A total of 16,804 limbs were injected by 98 investigators. Sclerotherapy was performed with 0.5% or 1% polidocanol for telangiectasias or spider veins, and with 3% polidocanol for varicose veins. The effectiveness of the sclerotherapy and any complications were reported during a 2-year period.


There were very few complications reported with polidocanol. There were no reported deaths or anaphylaxis. The investigators with previous experience of other sclerosants considered that the effectiveness of polidocanol was superior to STD (85%) and hypertonic saline (84%). Ninety percent of investigators considered that polidocanol had less frequent complications than STD, and 80% considered that these were less severe. Seventy-four percent considered that polidocanol had fewer side effects than hypertonic saline, and 74% considered that these were less severe.


Polidocanol is an effective sclerosant that has few complications.

[PubMed – indexed for MEDLINE]


Recent articles have introduced the novel concept of chemical lipolysis through local injections. Phosphatidylcholine is the active drug in the commercial preparation used for this purpose, but some studies have suggested that sodium deoxycholate, an excipient of the preparation, could be the real active substance.


We decided to investigate whether phosphatidylcholine and sodium deoxycholate have any clinicalefficacy in chemical lipolysis and their respective roles. We also studied the safety and side effects of
the treatments.

Thirty-seven consecutive female patients were studied for the treatment of localized fat in gynoid lipodystrophy. Each patient received injections of a phosphatidylcholine/sodium deoxycholate preparation on one side and sodium deoxycholate on the contralateral side, each single patient being herself the control. Four treatments were carried out every 8 weeks in a double-blind,  randomized fashion. Metric circumferential evaluations and photographic and ultrasonographic measurements throughout the study allowed for final judgment. A statistical evaluation concluded our study.


An overall reduction of local fat was obtained in 91.9% of the patients without statistically significant differences between the treated sides. Reduction values on the phosphatidylcholine/sodium deoxycholate–treated sides are in the order of 6.46% metrically and 36.87% ultrasonographically, whereas on the deoxycholate-treated sides they are in the order of 6.77% metrically and 36.06% ultrasonographically.
Both treatments, at the dose used in the study, proved safe in the short term. The most common side effects were local and few, but were more pronounced on the deoxycholate-treated sides.
No laboratory test was carried out.


Both treatments have shown moderate and equivalent efficacy in treating localized fat, with sodium deoxycholate having a slower postoperative resolution, suggesting that sodium deoxycholate could be sufficient by itself to determine fat cell destruction and that phosphatidylcholine could be useful for obtaining a later emulsification of the fat.
The authors have indicated no significant interest with commercial supporters.



We would like to announce that our webshop is getting a major update. New design, bug fixes (payment gateways), etc.

Currently accepted payment methods: Google checkout, Bank wire (EU), ACH (USA)  Paypal (in some cases only!) – future implementations will include Alertpay, Dotpay and Moneybookers.

You can still order via email at if you wish to use any other payment method!


NEW ARRIVAL: TB500 thymosin beta-4 recovery protein with performance enhancing properties $60 /5 mg

NEW ARRIVAL: IGF-1 lr3 1000 mcg $60

CICACTRICURE anti-wrinkle cream with peptides: $39



HYACETAM hyaluronic acid 5 ml 5%


CEREBROLYSIN 10 ml ampoules



What are growth factors?

A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation.  Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes.

Growth factors typically act as signaling molecules between cells. Examples are cytokines and hormones that bind to specific receptors on the surface of their target cells.  (

What does that mean?

Growth Factors are responsible for signaling our cells to make changes in our body, usually when repairing damaged cells or replacing dead cells.

How many growth factors are in the human placenta?

The human placenta contains potent amounts, over 128, rich growth factors.  Recent scientific research has shown that placenta is a rich healing and development agent for the body.  Inside the womb these growth factors are responsible for triggering cell mitosis (cell division) or the making of new cells.  Because the faetus grows at such a rapid rate many growth factors are needed to facilitate the growth process of the unborn baby’s organs, tissue, nerves, bones and the brain in such a short period of time.

Are growth factors necessary to heal after birth?

Yes, growth factors will play a large role in the bodies healing process after birth, however as we age our bodies produce less and less of these growth factors slowing our bodies natural regeneration processes.  As well, new mothers will be passing most of their body’s important nutrients to their new baby through the breast milk, leaving little nutrients for themselves. When the placenta is consumed after birth the rich growth factors give direct attention to damaged or developing tissue in the body, most importantly uterine, vaginal and breast tissue.  We believe these growth factors have a direct connection with the almost immediate slowing of blood loss after consumption of the raw placenta smoothie.  Mammals who consume the placenta never bleed after birth because they consume their entire placenta raw giving the body a large boost of the growth factors needed to heal the body completely and immediately.

What research has been done to prove these effects?

Mitogenic action of cytokines from placenta are shown to have physiological affects on the body including anti-inflammatory properties, regulation of the autonomous system, improvement of blood circulation, wound tissue healing, inhibition of protease, enhancement of nerve generation, balancing multiple hormone levels, immune boosting, analgesic effect and improvement of intestinal environment. (MFIII Human Placenta Injection, 2009)

Around the world many pharmaceutical companies are researching the benefits of using growth factors from human or animal placenta to aid in tissue regeneration.  MFIII Human Placenta Injection is sold on the Internet for a heavy price giving the public a chance to benefit from placenta extract for a wide range of health problems.  Famous footballers from UK premiership teams are being flown to countries like Switzerland and Serbia to have placenta injections to aid in the recovery process after serious injuries.  Placenta extract is also used in high end face creams and anti-aging balms and serums.

Research into placenta extract and the benefits of using growth factors for medicinal purposes is still ongoing however the benefits of using the placenta outside of the womb are now clear and only proves more why new mothers should consider keeping their rich organ for themselves.  After all, do we really know what the hospitals do with unwanted placentas???


FAQs about Lipo-dissolve

Phosphatidylcholine/Deoxycholate Overview

What are lipo-dissolve injections?

Lipo-dissolve injections have become an increasingly popular means to remove excess fat. The procedure goes by many names (e.g., Lipostabil®, Lipodissolve, Flab-Jab, Lipojection, Lipotherapy, etc.) and involves the injection of mixtures of various chemicals into the fat through multiple microinjections administered over multiple treatment sessions. The desired end result is the gradual removal of localized fat deposits. Lipo-dissolve injections are generally not regarded by medical professionals to be as potent as liposuction, a powerful yet invasive surgical procedure in which multiple liters of fat are ‘sucked’ from patients in a single session. Lipo-dissolve therapy typically requires that dozens of small ‘fat burning’ injections of compounded phosphatidylcholine/deoxycholate (PCDC) be injected into fat and connective tissue over several sessions. These drugs are not FDA-approved.

What are the compounds/ingredients in the injectable solution?

The main compound used in lipo-dissolve is phosphatidylcholine (PC), a compound derived from soy that is a component of cell membranes in many organisms, including humans.1 Deoxycholate (DC), a naturally occurring bile salt produced by the liver, is also used in the formulation to solubilize phosphatidylcholine, thus keeping it in solution.1 Together, the main ingredients are commonly abbreviated as PCDC, however without a specific FDA-approved formulation for the injected solution, the ratio of the two compounds in a given formulation may be substantially different depending on the provider. Some providers also add small amounts of other medications, vitamins, and herbs. PCDC injections have not been approved by FDA for ANY indication and neither phosphatidylcholine nor deoxycholate are active ingredients in ANY FDA-approved drug.
Where do providers get the PCDC for lipo-dissolve injections?

The PCDC drug is obtained from compounding pharmacies, which traditionally make small quantities of unique drugs for specialized treatments (e.g., special versions of drugs for patients with allergic reactions). According to experts who discussed this issue with the Washington Post, in many situations involving compounded drugs, quality control and sterility can often be “spotty or nonexistent.”2
What is the standard lipo-dissolve procedure?

There is no standard process/procedure that has been studied in controlled clinical trials or to the satisfaction of the FDA. Therefore, the procedure will differ depending on the provider. FDA-approved drugs have a standardized drug formula and method of administration. With lipo-dissolve, individual providers determine dosing and technique. The lipo-dissolve procedure “typically” involves an average of 2-4 treatment sessions spaced 4-8 weeks apart.3According to the Aesthetic Surgery Journal, the maximum safe dose of PC is 100 mL per session with approximately 0.4 mL delivered with every micro-injection. However, because studies have not concluded a standard protocol outlining specific number of sessions, number of microinjections per session, and amount of PC needed for results, this average may vary greatly.4
How is the drug cleared from the body?

There is no scientific support for theories about how the drug is cleared from the body. It is unclear exactly how the body metabolizes and excretes the drug and the broken down fat cells. The injected chemicals are believed to trigger an inflammatory response as the fat cells are broken down and are thought to be excreted in the urine and feces. Without pharmacologic studies (those that study the compound’s mechanism of action and are required for FDA-approved drugs), these theories cannot be confirmed.
How long has the procedure been around? How many times has it been performed?

Cosmetic use of phosphatidylcholine injections was introduced at the First International Meeting of Mesotherapy in 1988 by Italian Physician Sergio Maggiori5. The formulation began being used for fat removal in Brazil in the 1990’s yet was later banned by ANVISA (Brazilian National Agency of Health Inspection). The procedure has only more recently been introduced in the U.S., and the American Society of Non-surgical Aesthetics estimates that 50,000 to 100,000 lipo-dissolve treatments have been performed in the USA and Europe6. Despite the numbers of treatments performed, the drug’s safety and efficacy cannot be confirmed without controlled clinical trials as required by the FDA.
I keep hearing different terms for the treatment (e.g., lipo-dissolve, advanced lipo-dissolve, lipotherapy, injection lipolysis, etc.), are they all the same thing?

The treatments are similar in that each typically involves the injection of an unapproved PCDC formulation.

What areas can be treated with injections?

Currently, people use PCDC in a variety of areas (chin, abdomen, thighs). However, no well-controlled studies have examined where in the body the drug may or may not work. There is no FDA-approval for this drug for any part of the body.

Does the phosphatidylcholine affect other cells in the body besides fat cells?

It is unknown whether the drug affects other cells in the body (such as muscle or nerve cells). While a “theory” has been proposed for the method by which phosphatidylcholine destroys fat cells, the scientific mechanism still is not well understood.7
Are the injections a proper treatment for weight loss?

Without FDA-approval, this answer is unknown. But according to lipo-dissolve providers, the answer is no. Lipo-dissolve is not a viable means to lose weight. The ideal candidate is at a healthy weight but possesses localized fat deposits that cannot be reduced by exercise and diet. Lipo-dissolve may be successful in reducing inches but may not show any reduction in actual weight.
Are the ingredients used for lipo-dissolve safe?

PCDC is an unapproved drug. According to physicians currently studying the procedure, “until more safety data becomes available, physicians may be placing patients at unknown risks as they become reliant upon a compounded formulation for these treatments.”8 Additionally, FDA has stated that “there are no FDA approved drugs with an approved indication to dissolve fat and FDA cannot assure the safety and efficacy of these types of drugs.”8

FDA Status
Is the drug approved by the FDA?

PCDC is not approved by the FDA for any use. Furthermore, neither PC nor DC alone are active ingredients in any FDA-approved drug. FDA has issued a statement warning consumers “there are no FDA-approved drugs with an approved indication to dissolve fat and FDA cannot assure the safety and efficacy of these types of drugs”9 and that this is a “buyer-beware situation.”9
I understand that the compounds in PCDC are naturally occurring substances in our body. If it’s natural, why is it considered a drug?

Just because something is a naturally occurring substance does not mean that it is not a drug. Take insulin, adrenaline, human growth hormone, and erythropoietin, for example. They are natural substances in our body, all are considered drugs, and all are extremely dangerous at the wrong dose. The FDA considers something a drug if it affects the structure and function of the body. PCDC providers claim that it does just that.

What does FDA-Approval mean?

In the United States, prescription drugs are required to undergo rigorous laboratory, animal, and human clinical testing before they can be put on the market. The FDA reviews results of these studies to verify the identity, potency, purity, and stability of the ingredients as well to verify that the drug is safe and effective for its intended use. PCDC has not undergone any of the necessary testing required for FDA-approval. For more information on the drug approval process and the benefits of using drugs that have been FDA approved, please see the BOTOX®/Lipo-dissolve comparison page outlining the difference between an FDA-approved drug versus a non-FDA approved drug.

If PCDC is not approved, does that mean it’s being legally used off-label?

No. According to FDA, “off-label” use involves using an “approved” drug for an indication not in the approved labeling at the discretion of a physician10. Since PCDC is not approved, its use cannot be considered “off-label.” For more information, see Differences Between Lipo-dissolve and BOTOX® page.

Futhermore, the FDA has stated, “We are not aware of any phosphatidylcholine injectable products or sodium deoxycholate injectable products that could be used ‘off-label’ in ‘lipodissolve’ procedures.” Read more…

What data exists to demonstrate the safety and efficacy of phosphatidylcholine injections?

It is important to note that there have been numerous retrospective studies (i.e. historical observations) performed on the use of phosphatidylcholine injections for fat dissolution1,2and a few prospective non-placebo-controlled studies performed to test the efficacy of the procedure.11 However, to date there have been no prospective, placebo-controlled studies (those required for FDA approval) done on the use of PCDC for fat removal and therefore safety and efficacy cannot be confirmed. Placebo-controlled studies are those where participants are randomly assigned to receive either the placebo or the active substance. Neither the participant nor the doctor know which treatment the participant receives. The goal of this type of trial is to illustrate that it is the drug that is eliciting a response, not the placebo. With retrospective studies, one makes conclusions based on pre-existing data (i.e. you start with an answer and look backwards to selectively find data that supports your conclusion). Prospective trials, as required by the FDA, by their very structure prevent this from happening.




Recombinant myostatin (GDF-8) propeptide enhances the repair and regeneration of both muscle and bone in a model of deep penetrant musculoskeletal injury


Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.



Myostatin (GDF-8) is known as a potent inhibitor of muscle growth and development, and myostatin is also expressed early in the fracture healing process. The purpose of this study was to test the hypothesis that a new myostatin inhibitor, a recombinant myostatin propeptide, can enhance the repair and regeneration of both muscle and bone in cases of deep penetrant injury.


We used a fibula osteotomy model with associated damage to lateral compartment muscles (fibularis longus and brevis) in mice to test the hypothesis that blocking active myostatin with systemic injections of a recombinant myostatin propeptide would improve muscle and bone repair. Mice were assigned to two treatment groups after undergoing a fibula osteotomy: those receiving either vehicle (saline) or recombinant myostatin propeptide (20 mg/kg). Mice received one injection on the day of surgery, another injection 5 days after surgery, and a third injection 10 days after surgery. Mice were killed 15 days after the osteotomy procedure. Bone repair was assessed using microcomputed tomography (micro-CT) and histologic evaluation of the fracture callus. Muscle healing was assessed using Masson trichrome staining of the injury site, and image analysis was used to quantify the degree of fibrosis and muscle regeneration.


Three propeptide injections over a period of 15 days increased body mass by 7% and increased muscle mass by almost 20% (p < 0.001). Micro-CT analysis of the osteotomy site shows that by 15 days postosteotomy, bony callus tissue was observed bridging the osteotomy gap in 80% of the propeptide-treated mice but only 40% of the control (vehicle)-treated mice (p < 0.01). Micro-CT quantification shows that bone volume of the fracture callus was increased by ∼ 30% (p < 0.05) with propeptide treatment, and the increase in bone volume was accompanied by a significant increase in cartilage area (p = 0.01). Propeptide treatment significantly decreased the fraction of fibrous tissue in the wound site and increased the fraction of muscle relative to fibrous tissue by 20% (p < 0.01).


Blocking myostatin signaling in the injured limb improves fracture healing and enhances muscle regeneration. These data suggest that myostatin inhibitors may be effective for improving wound repair in cases of orthopaedic trauma and extremity injury.

[PubMed – indexed for MEDLINE]

AICAR BLOWOUT SALE! Contact us for purchase options

     100 mg: $45

     1000 mg: $350

     3 grams: $800

shipping: $20 flat rate worldwide

AICAR, aminoimidazole carboxamide ribonucleotide, acts as an agonist to AMP-activated protein kinase; AMP-activated protein kinase, also known as AMPK, is an enzyme with an important role in cellular homeostasis and energy regulation.[1]  AMPK acts through a variety of means to ultimately stimulate liver fatty oxidation, ketogenesis, beta-cell modulation of insulin secretion, and other functions within the body.  AICAR has been shown to stimulate glucose uptake and reduce apoptosis by reducing reactive oxygen compounds within cells.[2][3]

In a breakthrough study in 2008, Narkar et al of the Salk Institute discovered that AICAR significantly improves the performance of mice in endurance-type exercise by converting fast-twitch muscle fibers to the more energy-efficient, fat-burning, slow-twitch type. They also found that AICAR and GW1516, when given to “sedentary” mice, activated 40% of the genes that were turned on when mice were given GW1516 and made to exercise. As a result a publicity storm about “exercise pills” and “exercise in a pill” ensued.  The World Anti-Doping Agency now lists both compounds on their prohibited list (since 2009), and the lead researcher of the breakthrough study cooperated in providing data to make possible a urinalysis test to detect AICAR.[4][5]

Figure 5 Likely effects of AICAR (and other AMPK activators) on glucose homoeostasis in vivo

AICAR (1) stimulates glucose uptake into muscle through the membrane recruitment of Glut4, (2) inhibits hepatic glucose output and triacylglycerol synthesis, (3) inhibits both glucose uptake and lipolysis by adipose tissue, (4) acutely suppresses insulin release from pancreatic islets, and (5) activates glucose-responsive neurons in the paraventricular and arcuate nuclei of the hypothalamus, potentially stimulating appetite. Effects (1)–(4) probably explain the glucose-lowering effects of AICAR (and contribute to the effects of metformin and glitazones) and are likely to be beneficial in Type II diabetes. Effects (4) and (5) may be contra-indicated. FA, fatty acids.

AICAR has a number of other experimental/clinical and research chemical uses as it is expressed in a variety of tissue types.  Bai et al found that “data demonstrate that AICAR-initiated AMPK activation may represent a promising alternative to our current approaches to suppressing intestinal inflammation in IBD.”[6]

Guo et al found “results suggest[ing] a mechanism by which AICAR inhibits the proliferation of EGFRvIII expressing glioblastomas and point toward a potential therapeutic strategy for targeting EGFR-activated cancers.”[7]

An original study by Pold et al offers additional hope that AICAR could offer important treatment potential for humans:

Five-week-old, pre-diabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.[8]


[1]Corton JM, Gillespie JG, Hawley SA, Hardie DG. “5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells?”. Eur. J. Biochem. 229 (2): 558–65.  1995.

[2]Lemieux K, Konrad D, Klip A, Marette A. “The AMP-activated protein kinase activator AICAR does not induce GLUT4 translocation to transverse tubules but stimulates glucose uptake and p38 mitogen-activated protein kinases alpha and beta in skeletal muscle”. Faseb J. 17 (12): 1658–65. 2003.

[3]Kim JE, Kim YW, Lee IK, Kim JY, Kang YJ, Park SY.  “AMP-activated protein kinase activation by

5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) inhibits palmitate-induced endothelial cell apoptosis through reactive oxygen species suppression”. J. Pharmacol. Sci. 106 (3): 394–403. 2008.

[4]Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM. “AMPK and PPARdelta agonists are exercise mimetics”. Cell 134 (3): 405–15. 2008. [5]WADA 2009 Prohibited List: WADA PROHIBITED LIST PDF (PDF Document).

[6]Bai A, Yong M, Ma Y, Ma A, Weiss C, Guan Q, Bernstein C, Peng Z. Novel Anti-Inflammatory Action of 5-Aminoimidazole-4-carboxamide ribonucleoside with protective effect in DSS-induced acute and chronic colitis. J Pharmacol Exp Ther. 2010 Mar 17.

[7]Guo D, Hildebrandt IJ, Prins RM, Soto H, Mazzotta MM, Dang J, Czernin J, Shyy JY, Watson AD, Phelps M, Radu CG, Cloughesy TF, Mischel PS.  The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis.Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12932-7.

[8]Pold R, Jensen LS, Jessen N, Buhl ES, Schmitz O, Flyvbjerg A, Fujii N, Goodyear LJ, Gotfredsen CF, Brand CL, Lund S. Long-term AICAR administration and exercise prevents diabetes in ZDF rats.  Diabetes. 2005 Apr;54(4):928-34.

*The latter article is intended for educational / informational purposes only. THIS PRODUCT IS INTENDED AS A RESEARCH CHEMICAL ONLY. This designation allows the use of research chemicals strictly for in vitro testing and laboratory experimentation only. Bodily introduction of any kind into humans or animals is strictly forbidden by law.


The therapeutic effect of Cerebrolysin in the treatment of dementia and brain injury has been proposed because of neurotrophic properties of this compound. Since an increased kynurenine metabolism has been documented in several brain pathologies including dementia the aim of the present study was to investigate the biochemical properties of Cerebrolysin with respect to kynurenic acid (KYNA) formation in an in vitro study. KYNA is an endogenous metabolite of the kynurenine pathway of tryptophan degradation and is an antagonist of the glutamate ionotropic excitatory amino acid and of the nicotine cholinergic receptors. The activities of the KYNA synthesizing enzymes kynurenine aminotransferases I, II and III (KAT I, KAT II and KAT III) in rat liver, and rat and human brain homogenates were analysed in the presence of Cerebrolysin. KAT I, II and III activities were measured using a radio-enzymatic method in the presence of 1 mM pyruvate and 100 µM [H3]l-kynurenine. Cerebrolysin, dose-dependently and significantly reduced KAT I, KAT II and KAT III activities of rat liver homogenate. Furthermore, Cerebrolysin exerted a dose-dependent inhibition of rat and human brain KAT I, KAT II and KAT III activities, too. The inhibitory effect of Cerebrolysin was more pronounced for KAT I than for KAT II and KAT III. The present study for the first time demonstrates the ability of Cerebrolysin to lower KYNA formation in rat liver as well as in rat and human brain homogenates. We propose Cerebrolysin as a compound susceptible of therapeutic exploitation in some disorders associated with elevated KYNA metabolism in the brain and/or other tissues. We suggest that the anti-dementia effect of Cerebrolysin observed in Alzheimer patients could be in part due to Cerebrolysin induced reduction of KYNA levels, thus modulating the cholinergic and glutamatergic neurotransmissions.

Abbreviations: KYNA, kynurenic acid, KAT, kynurenine aminotransferase, NMDA, N-methyl-d-aspartate, EAA, excitatory amino acid, CNS, central nervous system

Keywords: Kynurenic acid, Kynurenine aminotransferases, NMDA receptor, Cholinergic receptor, Dementia, Cerebrolysin


Cerebrolysin Review
Wise Young, Ph.D., M.D.
W. M. Keck Center for Collaborative Neuroscience
Rutgers University, Piscataway, New Jersey 08540-8087
Originally posted 1 April 2006, minor revisions (10 Feb 2009)

Cerebrolysin is a peptide mixture isolated from pig brain. A neurotrophic peptidergic mixture produced by standardized enzymatic breakdown of lipid-free porcine brain proteins, cerebrolysin is composed of 25% low molecular weight peptides (<10K DA) and 75% free amino acids, based on free nitrogen content [1]. The mixture has relatively high concentrations of magnesium, potassium, phosphorus, and selenium [2], as well as other elements [3, 4]. While the drug has antioxidant properties, it is much less than trolox or vitamin E [5]. The active ingredient(s) in the mixture are not known. Two concentrates of the peptide fraction of cerebrolysin are being tested, one called EO21 and the other N-PEP-12 [6].

Multiple clinical trials have reported that cerebrolysin is beneficial in Alzheimer’s disease, stroke, and other neurological conditions. The drug has been studied since the early 1970’s. Double-blind placebo controlled trials have reported sustained improvements and slowing down of progressive memory loss, cognition impairment, mood changes, and motor and sensory symptoms of stroke and neurodegenerative diseases ( The drug has been approved for treatment of Alzheimer’s disease in the United States. Ebewe Pharmaceutical ( makes the drug. Over 176 articles have been published since 1973 on the subject of cerebrolysin treatment of various neurological disorders. I will review this literature below.

Chronic Stroke. In 1990, Ischenko & Ostrovskaia [26] compared the effects of cerebrolysin and various other agents on blood viscosity in 128 patients with circulatory encephalopathy. They found that cerebrolysin marked increased blood viscosity and suggesting that the drug be cautiously used in patients with ischemic blood circulation disorders. In Austria, Kofler, et al. [27] studied contingent negative variation (CNV) in 41 geriatric patients with moderate “organic brain syndrome” and showed that 10 infusions of cerebrolysin plus multi-vitamin infusions increased CNV amplitudes, compared to the placebo group that received multivitamin alone. Kofler, et al. also did psychometric measures in 27 patients with organic brain syndrome and treated with a course of ten cerebrolysin treatments, compared to 14 clinically comparable patients, showing significant improvements in the cerebrolysin treated group. In 1991, Vereschchagin, et al. [28] treated 30 patients with multi-infarct dementia and compared them with 30 patients that received placebo. Cerebrolysin improved memory, abstract thinking, and reaction time of the patients, confirmed with EEG-mapping. Pruszewicz, et al. [29] gave cerebrolysin to severe central hearing loss and observed improvement in 36%. In 1996, Iakno, et al. [30] treated 20 patients with vascular dementia and showed EEG effects and the most improvement in patients with the least cognitive deficit. In 2004, Gafurov and Alikulova [31] treated 2 groups of patients with ischemic brain hemispheric stroke and reported that cerebrolysin improved both groups.

Pediatric Treatments. Several Russian groups have been using cerebrolysin to treat neurological disorders in children. In 1998, Gromova, et al. [2] gave cerebrolysin to 36 3-8 year old children with minimal cerebral dysfunction. Gruzman, et al. [32] used intravenous cerebrolysin injections to treat resistant forms of night enuresis in children. In 2000, Sotnikova, et al. [33] found that cerebrolysin (1 ml per 10 kg) increased CD19+ cells and CD4+ lymphocytes with normalization of serum IgG and IgA levels and CD16+ cells (NK) at one month after treatment, in children (age 3-8 years) with minimal cerebral dysfunction; in addition, cerebrolysin activated T helper cells in vitro. Sukhareva, et al. [34] treated 120 children (age 4-15 years) with “neurosensory hypoacusis” with “pharmacopuncture” injecting cerebrolysin and several other drugs. They reported that the treatment improved speech intelligibility, headache, and other problems in 85% of cases. Sotnikova [35] gave cerebrolysin (1 ml/10kg) intramuscularly for one month to children with attention deficit syndrome, reporting that this resulted in “a simultaneous normalization of neurological and immune disorders and a reduction in the illness rate.” In 2003, Krasnoperova, et al. [36] gave cerebrolysin (0.1 ml daily for 5 days) to 19 children with childhood autism and 8 with Asperger’s syndrome (aged 2-8 ) and found positive effects in all the patients with Asperger’s syndrome and 89% of the patients with autism. Guseva and Dubovsakia [37] treated 646 children (age 8 weeks to 18 years) with optic nerve disease by giving retrobulbar cerebrolysin once daily, in combination with microcirculatory drugs, in the irrigation system, or just microcirculatory drugs alone through the irrigation system, reporting that cerebrolysin treatment improved vision.

Extrapyramidal hyperkinesis. This is a motor syndrome that results from neuroleptic (dopaminergic) drugs used to treat various neurological disorders including Parkinson’s disease, schizophrenia, and depression. In 1997, Kontsevoi, et al. [38] did an open-label study of cerebrolysin treatment of 30 Parkinson patients who had prolonged extrapyramidal complications from neuroleptic therapy, finding that cerebrolysin markedly reduced severity of extrapyramidal symptoms in 46.6% of the patients and partial response in 26.6%. In 1999, Panteleeva, et al. [39] gave cerebrolysin and magme B6 (a drug) to 51 patients with diagnoses of schizophrenia or depression, suffering from extrapyramidal and somato-vegetative effects of neuroleptic and anti-depressive drugs. Both drugs reduced the hyperkinetic and cardiovascular side effects of neuroleptic drugs. In 2004, Lukhanina, et al. [40] examined the effects of cerebrolysin on EEG activity of 19 patients with Parkinson’s disease and 18 healthy controls, They found twofold improvements in CNV mean amplitudes, strengthening of postexcitatory inhibition in the auditory system after paired stimulation, and other measures. An open-label prospective study in Russia assessed 25 patients with childhood autism (ages 3-8 ) who received 2 therapeutic courses of cerebrolysin. The patients all demonstrated a significant improvement in mental function, cognitive activity, attention during task performance, perception, and fine motor function [41].

Alzheimer’s Disease. In 1994, Ruther, et al. [42] did a double-blind placebo control study of cerebrolysin treatment of 120 patients with moderate Alzheimer’s dementia and found modest beneficial effects. In 1997, Rainer, et al. [43] treated 645 demented patients with 30 ml of cerebrolysin daily for an average of 17.8 days, reporting that the treatment improved clinical global impression in 80% of the patients and significantly more in younger and less afflicted patients. In 1998, several reviewers [44, 45] pointed out cerebrolysin as a potential therapy for Alzheimer’s disease. Windisch, et al. [46] called for clinical trials to ascertain whether cerebrolysin induces repair in chronic brain injury and whether the effects are long lasting. In 1999, Roshchina, et al. [47] found that cerebrolysin (30 ml) enhanced the beneficial effects of amridin (80 mg daily for 10 weeks) in 20 patients with Alzheimer’s, compared to 23 patients treated only with amiridin. In 2000, Bae, et al. [48] did a double-blind placebo-controlled multicenter study of cerebrolysin in 53 men and women with Alzheimer’s disease. They found that the cerebrolysin significantly improved cognitive deficits and global function in patients with mild to moderate dementia. Based on these results, Molloy and Standish [49] suggested that cerebrolysin be given to patients with Alzheimer’s disease. Ruther, et al. [50] evaluated 101 patients 6 months after completion of a 4-week course of 30 ml cerebrolysin or placebo, showing a clear sustained beneficial effect of cerebrolysin over placebo. Windisch [51] reviewed the literature and concluded that three placebo-controlled double-blind randomized studies had shown significant improvements of cognitive performance, global function, and activities of daily patients with Alzheimer’s disease, indicating a “powerful disease modifying activity” of cerebrolysin. In 2001, Ruether, et al. [52] did a 28-week, double-blind, placebo-controlled study of 4- week cerebrolysin treatment in 149 patients with Alzheimer’s disease, showing a 64.5% responder rate on the clinical global impression compared to 41.4% in the placebo group, as well as a 3.2 point difference in the ADAS-cog scale. The effects were maintained for 3 months after end of treatment. The treatment was repeated after a 2-month therapy-free period and improvements were maintained [53]. In 2002, Muresanu, et al. [54] showed that cerebrolysin improved activities of daily living in patients with Alzheimer’s disease. Panisset, et al. [55] randomized 192 patients with Alzheimer’s disease to cerebrolysin (30 ml, 5 days per week, 4 weeks) or placebo, finding that cerebrolysin is well tolerated and significantly improved global score for 2 months after end of active treatment. Gavrilova, et al. [56] correlated ApoE4 genotype in patients with mild-to-moderate Alzheimer’s disease and efficacy of cerebrolysin therapy and cholinergic (exelon) therapy. A 4-month treatment showed that 1.7 fold higher response rate to cerebrolysin than the exelon group but further analysis revealed that those with genotype ApoE4(-) had 3- fold higher effect from cerebrolysin than people with ApoE4(+) genotype. Roshchina, et al. [57] did a neuropsychological evaluation of Alzheimer patients treated with two doses cerebrolysin (10 or 30 ml) over 19 months. Patients receiving the higher dose showed better cognitive function and less disease progression. In 2006, Alvarez, et al. [58] did a 24-week double-blind placebo-controlled study of 10, 30, and 60 ml of cerebrolysin (5 days a week for the first four weeks and then 2 infusions per week for 8 weeks). The results indicate a reversed U-shaped dose response relationship. The 10 ml dose improved cognitive performance but, while the 30 and 60 ml dose did not further improve cognitive function, the higher doses showed significantly better global outcome impression scores. Thus, many clinical trials have confirmed long-term beneficial effects of cerebrolysin in people with Alzheimer’s disease.

Acute Stroke. In 1994, Gusev, et al. [59] treated 30 patients with acute ischemic strokes with daily intravenous doses of 10, 20, 30 ml for 10 days, reporting that the treatment accelerated recovery in those with moderate strokes, compared to control subjects. In 1995, Domzai & Zaleska [60] treated 10 patients with acute middle cerebral artery strokes with 15 mg/day of cerebrolysin for 21 days and found similar recovery compared to a larger group of 108 patients given other drugs. Sidorenko, et al. [61] treated patients with partial optic atrophy with retrobulbar injections of cerebrolysin and apparently saw “favorable” effects in 50% of cases, compared to only 25% of control untreated patients. In the same year, Koppi & Barolin [62, 63] compared 318 stroke patients that received standard hemodilution with 100 patients that received hemodilution with cerebrolysin; reporting the cerebrolysin accelerated recovery. In 1998, Funke, et al. [64] did a remarkable double-blind placebo-controlled study showing that cerebrolysin increased parietal EEG signal in 48 healthy subjects subjected to transient brain ischemia, comparing 10, 30, and 50 ml doses. In 2004, Skvortsova, et al. [65] randomized 36 patients (age 45-85 years) with ischemic stroke of the carotid territory to cerebrolysin (10 ml/day or 50 ml/day) or placebo on day 3 of the stroke. They found EEG improvement in 72.7% of the treated patients. Ladurner, et al. [66] randomized 146 patients to placebo or cerebrolysin within 24 hours after stroke and examined at various times up to 90 days later. While the cerebrolysin group showed no significant improvement in clinical neurological scores, the Barthel Index, or Clinical Global Impression when compared to the placebo Cerebrolysin Review – Wise Young – Page 6 group, patients on cerebrolysin showed significant better cognitive function on the Syndrome Short Test.

Other Conditions. Cerebrolysin has been reported to be beneficial in several other neurological conditions, including diabetic neuropathy, glaucoma, neurosurgical procedures, Rett syndrome, vascular dementia, and traumatic brain injury In 1997, Bisenbach, et al. [67] treated 20 patients with type II diabetes, giving them 20 ml of cerebrolysin-infusion daily over 10 days, comparing with an age matched placebo control group. Cerebrolysin treatment resulted in significant subjective improvement of painful diabetic neuropathy for at least 6 weeks. In 2000, Lunusova [68] used cerebrolysin to treat patients with persistent glaucoma, reporting that the treatment (along with others) arrested the glaucomatous process, improved visual acuity, and extended visual field. In 2000, Matula and Schoeggl [69] suggested that cerebrolysin may be useful for preventing neurological deficits such as confusion, disorientation, or cognitive deficits after neurosurgery. Deigner, et al. [70] suggested that cerebrolysin may act in neurodegenerative diseases by preventing neuronal apoptosis. In 2001, Gorbachevskaya, et al. [71] gave cerebrolysin to 9 girls with Rett syndrome (age 2-7 years). Treatment resulted in increased behavioral activity, attention level, motor function, and non-verbal social communication, as well as EEG. In 2001, Vereshchagin, et al. [72] gave cerebrolysin for 28 days (15 mg/day) annually for 2 years to 42 patients with vascular dementia in a double-blind placebo-controlled study. The trial suggested stabilization of cognitive loss and prevention of progression of vascular dementia. Alvarez, et al. [73] used cerebrolysin to treat patients with brain trauma and found significant improvement in patient’s clinical outcomes during the first year with no adverse events. In 2005, Wong, et al. [74] reported a beneficial effect of cerebrolysin on moderate and severe head injury patients. At 6 months after treatment, 67% of the patients in the cerebrolysin group attained good outcome (GOS 3-5) compared to a historical cohort. Cerebrolysin has been reported to be beneficial for a wide variety of neurodegenerative disorders [75, 76], organic mental disorders [77], multiple sclerosis [78], anti-aging [79], and ischemic encephalopathy [80].

Animal Studies

Early animal studies did not shed much light on the mechanism(s) of cerebrolysin. In 1975, Lindner, et al. [81] applied the hydrolysate to cultures of chick peripheral and central neurons and found that high concentrations reduced nerve fiber growth but increased migration of non-neuronal cells. Zommer & Kvandt [82] gave doses of 0.005-0.025 ml of cerebrolysin to neonatal rats and found earlier differentiation of cytoarchitectonic fields in cerebral cortex, as well as early accumulation and increase in granular secretions in the pituitary gland of the animals. In 1976, Trojanova, et al. [83] reported that single injections of cerebrolysin given intraperitoneally to rats did not change their resistance to anoxia but repeated (5x) dosing increased resistance of young female rats (35 day old) to anoxia and that higher doses also increased resistance of adult rats to anoxia, compared to control mixtures of amino acids, oligopeptides, and nucleotides.

Neural Development and Cerebral Metabolism. By the 1980’s, several groups reported the cerebrolysin affected neuronal development and cerebral metabolism in animals. In 1981, Wenzel, et al. [84] reported that cerebrolysin treatment significantly increased the number of dendritic spines in the dentate gyrus (hippocampus) of neonatal rats. In 1985, Windisch & Poiswanger [85] treated rats for 3, 5, 7 or 14 days and examined cerebral protein, lactic acid, and oxygen consumption of brain homogenates, finding that higher doses (2.5 ml/kg) significantly increased respiratory activity of the homogenates. These effects apparently were most prominent in young rats up to 4 weeks and then in older 12-18 month old rats [86].

Experimental Demyelination and Immune Modulation. In 1991, Bespalova, et al. [87] assessed brain cerebrosides, sulfocerebrosides and gangliosides in rats subjected to experimental demyelination and treated with cerebrolysin. Zuber [88] examined the effects of cerebrolysin on brain phospholipids in rats with experimental demyelination. In 1992, Belokrylov and Malchanova [89] reported that treatment with cerebrolysin increased the number of Thy-1 positive cells and in vivo immune responses. In 1998, Grechko [90] compared cerebrolysin with a number of other peptide immunomodulators drugs and found that cerebrolysin had greater effect on free open-field group behavior of animals than most.

Hippocampal lesions. In the early 1990’s, several groups studied the effects of cerebrolysin on recovery from fimbria-fornix lesions. In 1992, Akai, et al. [91] of Kinki University in Osaka, Japan examined the effects of cerebrolysin (FPF1070) on septal cholinergic neurons after transection of the fimbria-fornix in rat brain. They found that intraperitoneal injections of the aqueous mixture of protein-free solution (containing 85% free amino acid and 15% small peptides) stimulated growth of embryonic dorsal root ganglion cultures. Apparently, the FPF1070 mixture prevented degeneration and atrophy of injured cholinergic neurons. In 1996, Francis-Turner & Valouskova [92, 93] compared intraperitoneal cerebrolysin with different concentrations of intraventricular infusions with NGF and bFGF on amnesia induced by fimbria-fornix transections. Cerebrolysin treatment or cerebrolysin combined with bFGF eliminated retrograde amnesia in the rats. In 1998, Cruz, et al. [94] showed the cerebrolysin (2.5 mg/kg x 7 days) had only a modest effect on glutathione related enzymes after fimbria-fornix transection. However, Gonzalez, et al. [95] found that cerebrolysin preserved SOD and CAT activity in the brain after a septohippocampal lesion.

Blood-Brain Barrier. In 1995, Boado [96] at UCLA reported that cerebrolysin transiently increased the glucose transporter GLUT-1 expression in blood-brain-barrier (BBB) within 2 hours and then a reduction at 20-48 hours, suggesting that cerebrolysin modulates expression of BBB-GLUT-1 expression. Boado [97] then used a luciferin-luciferase reporter gene to show that cerebrolysin markedly increased the BBB-GLUT1 expression and that the mechanism did not involve phosphokinase C. In 1998, Boado [98, 99] showed that cerebrolysin increased GLUT-1 expression via mRNA stabilization. In 1999, Boado, et al. [100] showed that acute or chronic administration of cerebrolysin increases the transport of glucose from blood to brain. In 2000, Boado [101] further showed that cerebrolysin stabilized GLUT1 transporter mRNA by increasing p88 TAF. In 2000, Gschanes, et al. [102] showed that both cerebrolysin and its peptide fraction EO21 increased the abundance of GLUT1 transporter in the brains of both old and young rats. In 2001, Boado [103] showed that cerebrolysin markedly increases the expression of BBB-GLUT1 reporter genes containing regulatory cis-elements involved in stabilization and translation, increases glucose uptake by the BBB, and increases GLUT1 protein expression.

Hippocampal slices. In Toronto, Baskys, et al. [104] assessed cerebrolysin effects on hippocampal slices, finding that it suppressed synaptic responses in CA1 neurons but not dentate gyrus neurons. Xiong, et al. [105, 106] found that cerebrolysin caused presynaptic inhibition that can be blocked with adenosine A1 receptor blockers and, since cerebrolysin does not contain detectable amounts of adenosine, proposed that cerebrolysin acted indirectly perhaps be release of endogenous adenosine. Cerebrolysin also appears to inhibit hippocampal responses by activating the GABA-B receptor [107]. Meanwhile, in 1995, Zemkova, et al. [108] of the Czech Republic, found that cerebrolysin potentiates GABA-A receptors in culture mouse hippocampal slices and that this could be blocked by bicucullin (a GABA-A receptor blocker). Ischemia. In 1993, Sugita, et al. [109] assessed the effects of FPF1070 (cerebrolysin) on delayed neuronal death in the gerbil global ischemia model. They measured the formation of hydroxyl free radicals in the brain and found that both DMSO (a hydroxyl free radical scavenger) and FPF1070 significantly reduced delayed neuronal death and evidence of hydroxyl radicals in the brains, proposing that hydroxyl radical scavenging may be the mechanism of cerebrolysin effect. In 1996, Schwab, et al. [110] assessed the effects of cerebrolysin on cytoskeletal proteins after focal ischemia in rats. In 1997, Schwab, et al. [111] compared the effects of hypothermia and cerebrolysin, finding that the latter enhanced the neuroprotective effects of the former. Cerebrolysin also improved EEG signal and motor activity of rats after mild forebrain ischemia [112]. Gschanes, et al. [113] found that cerebrolysin improved spatial memory and motor activity in rats after ischemic-hypoxic injury. In 1998, Schwab, et al. [114] showed that cerebrolysin reduced the size of cerebral infarct and microtubule protein loss after middle cerebral artery occlusion. In 2005, Makarenko, et al. [115] compared different fractions of cerebrolysin on a bilateral hemorrhagic rat stroke model. They found the most pronounced effects for the cerebral-1 fraction and particularly the 1.2 subfractions.

Spreading depression, hypoxia, and hypoglycemia. In 1998, Bures, et al. [116] showed that cerebrolysin (2.5 mg/kg daily x 10 days) remarkably protected the hippocampus against damage during repeated spreading depressions. Koreleva, et al. [117] compared the effects of MK801 and cerebrolysin on focal ischemia, finding that cerebrolysin increased amplitude of evoked spreading depression. In the same year, Gannushkina, et al. [118] studied the effects of cerebrolysin on 389 rats after bilateral common carotid occlusion, showing that the treatment did not increase blood flow but increased EEG recovery that may enhance ischemia damage. In 1999, Buresh, et al. [119] reported that cerebrolysin completely prevented hypoxia induced loss of CA1 neurons in the hippocampus. Koroleva, et al. [120] found that cerebrolysin treatment protected the hippocampus against carbon monoxide poisoning and spreading depression. In 2000, Veinbergs, et al. [121] pre-treatment with cerebrolysin was necessary to provide significant neuroprotection for kainic acid injections. In 2003, Patockova, et al. [122] showed that cerebrolysin significantly reduced lipid peroxidation induced by insulin hypoglycemia in the hearts and brains of mice.

Alzheimer’s disease. In 1999, Masliah, et al. [123] showed that cerebrolysin ameliorates performance deficits and neuronal damage in apolipoprotein E-deficient mice (a model of Alzheimer’s disease). In 2002, Rockenstein, et al. [124] treated transgenic mice expressing human amyloid precursor protein (APP751) under the Thy-1 promoter. Cerebrolysin significantly reduced the amyloid burden in the frontal cortex of 5-month-old mice, as well as the levels of A-beta (1-42). In 2003, Rockenstein, et al. [125] showed that cerebrolysin is neuroprotective in a transgenic mouse expressing human mutant amyloid precursor protein (APP) under the Thy1 promoter, start 3 or 6 months after birth. The treatment significantly ameliorated performance deficits and protected neurons. Rockenstein, et al. [126] investigated various gene expression and found no change in BACE1, Notch1, Nep, and IDE but did find higher levels of active cyclin-dependent kinase-1 (CDK5) and glycogen synthetase kinase-3 beta (GSK3beta).

Memory. In 1996, Hutter-Paier, et al. [127-130] reported that a single injection of cerebrolysin improved passive avoidance reactions in rats after transient cerebral ischemia. Gschanes & Windisch [131] likewise found that cerebrolysin improved spatial navigation in rats after transient brain ischemia. In 1998, Gschanes and Windisch [132] assessed the effects of cerebrolysin on spatial navigation in old (24-month) rats and found that cerebrolysin and EO21 (the concentrated peptide fraction of cerebrolysin) both improved spatial learning and memory of the rats. In 1999, Gschanes and Windisch [133] found that cerebrolysin or EO21 also improved spatial learning and memory in young rats, lasting up to 3 months after treatment stopped. In 1998, Valouskova and Francis- Turner [134] reported that cerebrolysin restored learning capability in rats when given 4 months after brain lesions. In 1999, Reinprecht, et al. [135] gave cerebrolysin or EO21 to 24-month old rats and found that the peptide mixtures improved cognitive performance of the rats and increased number of synaptophysin-immunostaining in the hippocampus. In 1999, Valouskova and Gschanes [136] compared NGF, bFGF, and cerebrolysin on rat performance in the Morris water maze test after bilateral frontoparietal cortical lesions, showing that cerebrolysin had a significant beneficial effect that declined to control levels by 8 months. Windolz, et al. [137] found that cerebrolysin or EO21 increased synaptophysin immunoreactivity in the brains of 6-week old rats. Eder, et al. [138] reported that cerebrolysin increased expression of the glutamate receptor subunit 1 (GluR1).

Spinal Motoneurons and Injury. Haninec, et al. [139] reported that insulin-like growth factor I (IGF-I) and cerebrolysin improves survival of motoneurons after ventral root avulsion. Either IGF-1 or cerebrolysin were effective when given intrathecally to the spinal cord. In 2004, Haninec, et al. [140] showed that BDNF and cerebrolysin both increased reinnervation of the rat musculocutaneous nerve stump after avulsion and its direct reconnection with the C5 spinal cord segment. BDNF was better than cerebrolysin. In 2005, Bul’on, et al. [141] studied the effects of cytoflavin or cerebrolysin in rats after spinal cord compression injury. The neuroprotective effects of cytoflavin were greater than for cerebrolysin.

Cell Cultures. In 1998, Hutter-Paier, et al. [142] showed that cerebrolysin counteracted the excitotoxic effects of glutamate and hypoxia [143] in cultured chick cortical neurons. In 1999, Lombardi, et al. [144] applied cerebrolysin to cultures of rat astrocytes and microglia, showing that the peptide mixture prevented microglial activation after LPS activation and reduced interleukin-1b expression. Mallory, et al. [145] reported that cerebrolysin applied to the human teratocarcinoma cell line (NT2) markedly increased expression of synaptic-associated proteins, suggesting that it has synaptotrophic effects mediated through regulation of APP expression. Alvarez, et al. [146] likewise showed that cerebrolysin reduced microglial activation both in vitro and in vivo. Satou, et al. [147] reported that cerebrolysin had a inverted U-dose response on neurite growth and suggested that cerebrolysin has different effects depending on the subpopulation of neuron. Wronski, et al. [148] showed that cerebrolysin prevented MAP2 loss in primary neuronal cultures after brief hypoxia. Cerebrolysin also inhibits the calcium-dependent protease calpain [149]. In 2001, Hartbauer, et al. [1] showed that cerebrolysin is anti-apoptotic in embryonic chick cortical neuronal cultures and stimulates outgrowth and protection of neurites [150]. In 2002, Gutmann, et al. [151] showed cerebrolysin protects cultured chick cortical neurons from cell death from a wide variety of causes, including glutamate, iodoacetate, and ionomycin; they propose that cerebrolysin stabilizes calcium ionic homeostasis. Safarova, et al. [152] showed that cerebrolysin improved survival of PC12 cells in serum-free medium, reducing apoptosis from 32% to 10%. In 2005, Schauer, et al. [153] found that a single addition of cerebrolysin to culture medium resulted in significant protection of tissue cultures against ischemia and hypoxia for up to 2 weeks. The treatment can even be delayed as long as 96 hours and still have beneficial effects. In 2006, Riley, et al. [154] applied cerebrolysin to organotypic brain slices and showed that the most pronounced neuroprotective effects of other drugs was seen when the drug was added both before and after glutamate.

Discussion and Summary

On the surface, cerebrolysin seems to be the worst sort of “drug” to investigate. First, it is not clear what cerebrolysin actually contains. Second, it is difficult to imagine why an intravenous injection of an extract of enzyme-digested pig brain proteins, composed of 25% low molecular weight peptides and 75% free amino acids, would be helpful. While we know that many peptides and amino acids act as growth factors and neurotransmitters, the blood brain barrier prevents the movement of peptides and amino acids from the blood to the brain. Third, if peptides and amino acids readily crossed the blood brain barrier, our brains would be subject to the whims of every steak and meal that we eat.  Finally, cerebrolysin is digested proteins from pig brain. It should be quite immunogenic to inject all these foreign peptides intravenously. Immunogenic reactions are complex and not well understood. Thus, in theory and from the viewpoint of safety, cerebrolysin should not only be ineffective but may pose significant risks.

Early 1970’s anecdotal clinical reports in Russia did not contribute to the credibility of cerebrolysin. It was being used in patients with cerebral arteriosclerosis, infantile cerebral palsy, and dementia. None of the studies were adequately controlled and the outcomes were vague and it all just seemed too good to be true. Likewise, early animal and cell culture studies likewise did not provide much information. However, in Russia, cerebrolysin was widely used and tried on many different kinds of diseases, mostly hopeless and poorly documented. This is of course a natural tendency. If a safe and effective therapy exists for a condition, that therapy would of course be the first choice of doctors. Conditions that have no known effective therapies are the ones that are most likely to be treated by cerebrolysin.

Animal studies turned the tide of skepticism. In the early 1980’s, the work of Wenzel, et al. [84] showing changes in neuronal synapses and Windisch & Poiswanger [85] reporting dose-related effects of cerebrolysin on cerebral metabolism suggested that the hydroxylate was doing something to the brain. Cerebrolysin also appeared to affect brain phospholipids [88] and may even have some effects of the immune system [89]. By the 1990’s, several groups reported remarkable effects of cerebrolysin on hippocampal lesions, preventing degeneration and atrophy of cholinergic neurons [91] and amnesia [92, 93], In 1995, Boado [96] showed that cerebrolysin remarkably upregulates the glucose transporter in the blood brain barrier, through a specific mechanism involving stabilization of the GLUT1 mRNA and associated not only with increase in GLUT1 protein but also increased glucose transport across the blood-brain-barrier [100].

Many clinical trials have now reported that cerebrolysin is an effective and safe therapy for many neurological disorders, ranging from stroke to Alzheimer’s disease. The drug’s primary effect seems to be on hippocampal function. Some studies suggest that cerebrolysin may be modestly neuroprotective in stroke and facilitates recovery from stroke. The side effects of the drug seem to be negligible. There are efforts underway to develop an oral version of the drug but the vast majority of the studies involve daily intravenous injections. The apparently broad spectrum of neuroprotective and neuroreparative effects of the drug both in the acute and chronic phases of brain injury suggest that this drug should be useful for both acute and chronic stroke and traumatic brain injury. Several studies suggest that the drug stabilizes excitability of the brain and can reduce hyperkinetic syndromes associated with neuroleptic drugs used for Parkinson’s disease. It may also be useful for preventing progressive deterioration in Parkinson’s disease although no clinical trial has addressed this issue yet.

An impressive array of clinical trials support beneficial effects of cerebrolysin on Alzheimer’s disease, beginning with Ruther, et al. [42] with 120 patients in 1994 and Rainer, et al. [43] with 645 patients in 1997. In 1999, Roshchina, et al. [47], Bae, et al. [48], and Ruther, et al. [50] confirmed these results. The effects of the cerebrolysin are not only statistically but also clinically significant [54]. The cerebrolysin responder rate on global clinical impression scale was 64.5% compared to 41.4% in placebo treated patients [52]. Several clinical trials also showed a clear dose-response [58] and several animal studies [6] are suggesting that the active ingredient is in the peptide fraction and not the amino acid fraction of cerebrolysin. People with genetic causes of the disease appear to be more responsive to cerebrolysin [56]. More interesting, the drug effects appear to last many months or even years after treatment has stopped [52, 53, 55]. This long-lasting effects suggest that cerebrolysin is not merely improving the balance of neurotransmitters or increasing the excitability of neurons, although EEG studies suggest that changes of excitability do occur with cerebrolysin treatment. Thus, it seems that cerebrolysin may be stimulating repair or perhaps even neuronal replacement in the brain. One interesting possibility is the cerebrolysin may be stimulating stem cells in the brain and repair processes that we do not understand.

Some clinical evidence suggest that cerebrolysin may be beneficial for other neurological conditions, including extrapyramidal hyperkinesis associated with neuroleptic therapy [38-40], with acute [65, 66] and chronic [28, 30, 31] stroke, diabetic neuropathy [67], Rett syndrome [71], vascular dementia [72], brain trauma [73, 74], organic mental disorders [77], multiple sclerosis [78], anti-aging [79], ischemic encephalopathy [80], and other neurodegenerative disorders [75, 76], Little data is available concerning the effect of the drug on spinal cord injury. Only one recent study is available regarding cerebrolysin therapy of a rat spinal cord compression model and it suggests a modest effect of the drug compared to another antioxidant. More studies are needed to ascertain the benefits of cerebrolysin for both acute and chronic spinal cord injury.