INTRODUCTION:

Agmatine is an endogenous amine formed by the enzymatic decarboxylation of L- arginine by arginine decarboxylase, has been discovered recently in mammals. Agmatine acts as a novel neurotransmitter or neuromodulator in the central nervous system that binds with high affinity to α2- adrenergic and imadazoline receptors [1]. In addition agamatine inhibits N-methyl -D-aspartate (NMDA) receptors and all isoform of nitric acid synthase (NOS) in the brain [1]. In the body, Agmatine is widely and unevenly distributed. It has been identified in the stomach, aorta, small intestine, large intestine, spleen, lung, vas deferens (of the male genital tract), adrenal gland, kidney, heart, liver, skeletal muscle, the testes, and brain. The concentration of agmatine varies in different parts of these organs. [2]

Structure of agmatine:

Formation of Agmatine:

As mentioned above agmatine is produced in the body from the action of enzyme arginine decarboxylase which converts L-arginine to agmatine [2]. However as the activity of the enzyme is rather low, other roots of agmatine are.

1. Agmatine is formed and released in high amounts through bacteria in the guts and through pathogens in our body.

2. Ingested food.

3. Transformed gastrointestinal cells.

4. Through circulation from liver.

Generally meats, fish and shellfish contain high level of agmatine. It is also present in fairly high amount in processed, fermented food such as beer and shake.

Mechanism of action of Agmatine:

Agmatine is an interesting compound because it can act as a signal triggering molecule by binding to certain receptors in the body. Example of receptors is imidazoline receptors and the α2-adrenoreceptors. Imidazoline receptors are classified into three groups and agmatine can induce all three. Contingent on the receptor agmatine can help in

· Lowering of blood pressure

· Transition of pain and proffer neuroprotection

· Modulation of insulin release

Agmatine has also shown to function as an antidepressant and in several animals studies to be possible therapeutic treatment for cancer, diabetes, brain and spinal cord injuries as well as neurodegenerative conditions such as Alzheimer’s and dementia[2].

Treatment of traumatic brain injury by agmatine therapy:

Traumatic brain injury (TBI) is a major burden for the families and the community in terms of cost, suffering, and disability in all developed countries. TBI is the second largest killer in the world after conventional stroke. In spite of the seriousness of this problem, neuroprotective drugs available for those suffering with TBI [3].

Evidence has accumulated to suggest that both nitric oxide (NO) and glutamate contribute to hypoxia-ischemia brain injury [4]. Inhibitors of nitric oxide synthase (NOS) and antagonists of N-Methyl-D-aspartate (NMDA) glutamate receptors are neuroprotective in hypoxia-ischemia brain injury. Agmatine is thought to be synthesised in the mammalian brain [4]. Agmatine is able to inhibit all isoform of NOS [5, 6] as well as the NMDA subclass of glutamate receptors [7, 8]. Treatments with agmatine are neuroprotective in both rat ischemic brain injury [9] and rat spinal cord injury [10].

Action of Agmatine on the body of athlete:

Ø Agmatine is a pain fighter it benefits an athlete in two ways.

a) It can increase the ensue of analgesics used during recovery from [11] Injury.

b) It has the potential to aid in post work-out recovery.

Ø Agmatine enhances insulin production leading to better insulin response. This allows a positive effect in attaining body composition goals. Higher insulin response produces a better muscular body.[11]

Ø Agmatine can react on different hypothalamic and pituitary hormones like luteinising hormone and growth hormone. It controls the hormonal environment of the athlete and make them look and feel better.

Ø Agmatine relieves anxiety and it has antidepressant properties which help in controlling the cortisol level in the stressful life of an athlete.

Ø Agmatine helps in the modulation of nitric oxide(NO) and stimulation of nitric oxide synthase(NOS) which intern is essential for th proper functioning of polyamine biosynthetic pathway.[11]

Ø Agmatine reacts on cathacolamine like epinephrine, nor epinephrine and dopamine. These compounds play a major role in the life of athlete. They help in energy production and aid in animation of stress produced by competition.

Ø Agmatine also plays a role as an antioxidant. The stress the body takes up when an athlete is in gym or field could ultimately have effect on build up. Agmatine can offer protection from the undesired effects of free radicals on the body.

Ø Agmatine can also act as novel neurotransmitter. This indeed gives athletes a potential mental edge to prepare for various events.

Ø Agmatine aids in kidney function by the alteration of glomerular filtration rate (GFR). This helps in the removal of various nitrogenous waste products.[11]

Ø Agmatine also has a hypertensive role in which it helps to keep the blood pressure in check.

Role of agmatine in kidney function:

Kidney expresses an mRNA for the enzyme that produces agmatine which is argentinine decarboxylase. The kidney also contains agmatine and imidazoline receptors that bind agmatine. In the recent study from the laboratory of Blantz et al., administration of agmatine into the renal interstitium and into the urinary space of surface glomeruli of Wistar-Fromter significantly increased the single nephron glomerular filtration rate (SNFGR) and absolute proximal reabsorption rate in surface nephrons [12].

A major effect of agmatine maybe to inhibit the calcium-sensitive nitric oxide synthase within the kidney [13]. It is possible that the effect protects the cells from self-destruction by preventing nitric oxide from inhibiting mitochondrial function. This raises the interesting possibility that agmatine functions in an anticrime role to guard against overproduction of nitric acid while functioning in peregrine role in adjacent cells to produce nitric oxide.

Salt of agmatine – agmatine sulphate:

Animal study demonstrates that agmatine sulphate, the commonly used salt of agmatine, is absorbed by the gastrointestinal tract and distributed in the body, and that it crosses the blood brain barrier. Of specific interest, is the substantial pre-clinical body of evidence demonstrating the beneficial effects of agmatine on the nervous system? These include neuroprotection, neuropathic pain reducing effect and anti-anxiety and anti depressive effect.

Agmatine benefit for body building:

Agmatine is used in bodybuilding as a supplement to help in the quest for increased muscle mass. It improves the mind muscle connection to improve the contractive efforts our muscle [11].

Agmatine possible ability to regulate insulin production and increase the uptake of glucose may offer benefits for glycogen storage as well as downgrade in the amount of glucose being transformed into fat [11].

Disadvantages and side effects of agmatine:

Agmatine is relatively saved to use even at high doses and seems to have very low toxicity in cells. In the first clinical trial of agmatine there were few side effects like moderate diarrhoea and mild nausea.

CONCLUSION:

Hence it can be concluded that the amine agmatine has many beneficial effects on the body. It binds with imidazoline receptors and help in lowering of blood pressure, it acts as neurotransmitter; it plays a role in antioxidant and helps in energy production especially in athletes. The salt of agmatine which is agmatine sulphate also plays a major role in anti-depressing effects.

REFERENCES:

1. D.J.Reis, S.Regunathan, is agmatine a novel neurotransmitter in brain. Trends pharmacol. Sci. 21(2000) 187-193.

2. Royal G, fat loss supplements-agmatine vol-4, 556-559, (2000) - retrieved from www. Mrsupplement,gov.in.au/agmatine

3. Sahuquillo j, poca MA, Amros S. Current effect of pathophsiology and cell dysfunction after severe head injury. Cur harm des 2001; 7:1475-2003.

4. Cain Z, Xiao F, Fratkin JD, et al protection of neonatal rat brain from hypoxic-ischemic injury by LY379268, a group II metabotrophic glutamate receptor agonist. Neuroreport 1999; 10:3929-31.

5. Abe K, Abe Y, Saito H. Agmatine suppresses nitric oxide production in microglia. Brain Res 2000; 872:141—8.

6. Demady DR, Jianmongkol S, Vuletich JL, et al. Agmatine enhances the NADPH oxidase activity of neuronal NO synthase and leads to oxidative inactivation of the enzyme. Mol Pharmacol 2001; 59:24—9.

7. Yang XC, Reis DJ. Agmatine selectively blocks the Nmethyl- D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther1999;288:544—9.

8. Olmos G, DeGregorio-Rocasolano N, Paz Regalado M. Protection by imidazol(ine) drugs and agmatine of glutamate induced neurotoxicity in cultured cerebellar granule cells through blockade of NMDA receptor. Br J Pharmacol 1999; 127:1317—26.

9 Gilad GM, Salami K, Ramey JM, et al. Agmatine treatment Neuroprotective rodent brain injury models. Life Sic 1996; 58:PL41—6.

10 YU CG, Marcello AE, Fairbanks CA, et al. Agmatine improves locomotors Function and reduces tissue damage following spinal cord injury.Neuroreport 2000; 11:3203-7.

11 Joey Rodriguez and Dryden Houser, MD, MHSA.

Www. Bodybuilding.com/agmatine.

12 Morrissey j. McCracken R, ishidoya s, Lahr S. Partial cloning and Characterization of an arginine decarboxylase in the kidney. Kidney Into 1995; 47: 1458-1461.

13 Lorie MJ, Novotny WF, PETERSON OW et al. Agmatine a bioactive Metabolite of arginine; production, degradation and functional effect on the kidney of rats.

Received on 30.07.2013 Modified on 10.09.2013

Research J. Pharm. and Tech. 7(1): Jan. 2014; Page 95-97