Skip to main content Accessibility help
×
Home
Hostname: page-component-768dbb666b-dkbpd Total loading time: 0.416 Render date: 2023-02-04T07:18:56.767Z Has data issue: true Feature Flags: { "useRatesEcommerce": false } hasContentIssue true

The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study

Published online by Cambridge University Press:  26 February 2013

Baron Shopsin*
Affiliation:
Former Chief, Unit for The Study and Treatment of Affective, Disorders, & Lithium Clinic, Neuropsychopharmacology Research Section, Department of Psychiatry, NYU Medical Center, and Associate Professor of Psychiatry, NYU School of Medicine, USA
*
Baron Shopsin, MD,PO Box 2054, Ponte Vedra Beach, Florida 32004, USA. E‐mail: baronius01@aol.com

Abstract

Objectives

To examine and record the clinical antidepressant effect of exogenous agmatine, an amino acid derived central glutamaergic modulator in endogenously depressed subjects. It was also the author's intention to examine the effects of parachlorophenylalanine (PCPA) in therapeutic responders to determine if serotonergic mechanisms mediate agmatine's antidepressant effect.

Methodology

Exogenous agmatine was ingested in doses of 2‐3mg/day by depressed subjects with Major Depresssive Disorder (MDD), clinically assessed using the 21 item Hamilton Rating Scale for Depression (HAM‐D), the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS). Antidepressant responders volunteered to concommittantly ingest parachlorophenylalanine (PCPA) at starting doses of 250mg/day, and increased until depressive relapse, mitigating side effects, or a maximum dosage of 1250mg/day.

Results

Three depressed subjects showing total illness remission with exogenous agmatine did not relapse after concomitantly adding PCPA. Effective in relieving both psychomotor agitation and retardation, the antidepressant effect was free of physical or behavioural side effects: gastrointestinal discomfort and loose stools in one subject resolved spontaneously within days. All three subjects refused to risk depressive relapse by temporarily stopping agmatine after PCPA was stopped.

Conclusion

The antidepressant effect of exogenous agmatine was documented in a small number of MDD subjects, and was not reversed/modified by PCPA confirming findings in animals that therapeutic response is not mediated by serotonergic mechanisms. A NAMDA (N‐methyl‐D‐aspartate) receptor antagonist, agmatine's recognized function in brain as inhibitory modulator of excitatory glutamatergic transmission suggests a pivotal role for brain glutamate, contributing to the ripening glutamatergic basis of depression, and a rational basis for future antidepressant pharmacotherapy.

Type
Original Articles
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

He remains clinically active and maintains a private practice.

[Correction added on 2 August 2012, after first online publication: The affiliation was updated to indicate that the author is the former chief of the stated affiliation and an associate professor of psychiatry who currently remains clinically active with a private practice.]

References

1Sastre, M, Regunathan, S, Galea, E, Reis, DJ. Agmatinase activity in rat brain: a metabolic pathway for the degradation of agmatine. J Neurochem 1996;67:17611765. Epub 1996/10/01.CrossRefGoogle ScholarPubMed
2Regunathan, S, Feinstein, DL, Raasch, W, Reis, DJ. Agmatine (decarboxylated arginine) is synthesized and stored in astrocytes. Neuroreport 1995;6:18971900. Epub 1995/10/02.CrossRefGoogle ScholarPubMed
3Yang, XC, Reis, DJ. Agmatine selectively blocks the N‐methyl‐D‐aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther 1999;288:544549. Epub 1999/01/26.Google ScholarPubMed
4Wang, WP, Iyo, AH, Miguel‐Hidalgo, J, Regunathan, S, Zhu, MY. Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons. Brain Res 2006;1084:210216. Epub 2006/03/21.CrossRefGoogle ScholarPubMed
5Feng, Y, LeBlanc, MH, Regunathan, S. Agmatine reduces extracellular glutamate during pentylenetetrazole‐induced seizures in rat brain: a potential mechanism for the anticonvulsive effects. Neurosci Lett 2005;390:129133. Epub 2005/08/30.CrossRefGoogle ScholarPubMed
6Wegener, G, Mathé, AA. Nitric oxide signaling in depression and antidepressant action. Neurobiology of depression. CRC Press, Taylor & Francis Publishing Group, London, UK 2011:341370.Google Scholar
7Abe, K, Abe, Y, Saito, H. Agmatine suppresses nitric oxide production in microglia. Brain Res 2000;872:141148. Epub 2000/08/05.CrossRefGoogle ScholarPubMed
8Qiu, WW, Zheng, RY. Neuroprotective effects of receptor imidazoline 2 and its endogenous ligand agmatine. Neurosci Bull 2006;22:187191. Epub 2007/08/21.Google ScholarPubMed
9Ahn, SK, Hong, S, Park, YM, Lee, WT, Park, KA, Lee, JE. Effects of agmatine on hypoxic microglia and activity of nitric oxide synthase. Brain Res 2011;1373:4854. Epub 2010/12/15.CrossRefGoogle ScholarPubMed
10Gorbatyuk, OS, Milner, TA, Wang, G, Regunathan, S, Reis, DJ. Localization of agmatine in vasopressin and oxytocin neurons of the rat hypothalamic paraventricular and supraoptic nuclei. Exp Neurol 2001;171:235245. Epub 2001/09/28.CrossRefGoogle ScholarPubMed
11Shopsin, B, Friedman, E, Gershon, S. Parachlorophenylalanine reversal of tranylcypromine effects in depressed patients. Arch Gen Psychiatry 1976;33:811819.CrossRefGoogle ScholarPubMed
12Krass, M, Wegener, G, Vasar, E, Volke, V. Antidepressant‐like effect of agmatine is not mediated by serotonin. Behav Brain Res 2008;188:324328. Epub 2008/01/08.CrossRefGoogle Scholar
13Shutoh, F, Hamada, S, Shibata, M et al. Long term depletion of serotonin leads to selective changes in glutamate receptor subunits. Neurosci Res 2000;38:365371. Epub 2001/02/13.CrossRefGoogle ScholarPubMed
14Sierralta, F, Pinardi, G, Miranda, HF. Effect of p‐chlorophenylalanine and alpha‐methyltyrosine on the antinociceptive effect of antidepressant drugs. Pharmacol Toxicol 1995;77:276280. Epub 1995/10/01.CrossRefGoogle ScholarPubMed
15Diazgranados, N, Ibrahim, LA, Brutsche, NE et al. Rapid resolution of suicidal ideation after a single infusion of an N‐methyl‐D‐aspartate antagonist in patients with treatment‐resistant major depressive disorder. J Clin Psychiatry 2010;71:16051611. Epub 2010/08/03.CrossRefGoogle ScholarPubMed
16Zarate, CA Jr, Singh, JB, Carlson, PJ et al. A randomized trial of an N‐methyl‐D‐aspartate antagonist in treatment‐resistant major depression. Arch Gen Psychiatry 2006;63:856864.CrossRefGoogle ScholarPubMed
17Ibrahim, L, Diazgranados, N, Franco‐Chaves, J, Kronstein, P et al. Course of Improvement in Depressive Symptoms to a Single Intravenous Infusion of Ketamine vs Add‐on Riluzole: results from a 4‐Week, Double‐Blind, Placebo‐Controlled Study. Neuropsychopharmacology 2012;37:15261533.CrossRefGoogle ScholarPubMed
18Zarate, CA, Manji, HK. Riluzole in psychiatry: a systematic review of the literature. Expert Opin Drug Metab Toxicol 2008;4:12231234. Epub 2008/08/30.CrossRefGoogle ScholarPubMed
19Zarate, CA Jr, Payne, JL, Quiroz, J et al. An open‐label trial of riluzole in patients with treatment‐resistant major depression. Am J Psychiatry 2004;161:171174. Epub 2004/01/02.CrossRefGoogle ScholarPubMed
38
Cited by

Save article to Kindle

To save this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study
Available formats
×

Save article to Dropbox

To save this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about saving content to Dropbox.

The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study
Available formats
×

Save article to Google Drive

To save this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you used this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about saving content to Google Drive.

The clinical antidepressant effect of exogenous agmatine is not reversed by parachlorophenylalanine: a pilot study
Available formats
×
×

Reply to: Submit a response

Please enter your response.

Your details

Please enter a valid email address.

Conflicting interests

Do you have any conflicting interests? *