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Agmatine & Imidazoline Receptors: A brief pharmacological review

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Agmatine [wiki] is an endogenous imidazoline receptor ligand which also inhibits N-methyl-D-aspartate (NMDA) receptors, nicotinic acetylcholine receptors, nitric oxide synthase enzymes, K+ and Ca2+ channels, along with possessing action at α2-adrenergic and certain serotonin receptors [MoA].

Agmatine induces significant (but non-serotonin dependent [1]) antidepressant [2, 3] and anxiolytic effects [2, 4] It additionally modulates (via imidazoline receptors) the antidepressant effects of SSRIs [5] and ethanol induced anxiolysis [6]. Perhaps most interesting is that, in mice, it potently enhances the antidepressant effects of NMDA antagonists, along with those of conventional antidepressants [7]. It also synergises (itself being potentially effective as an analgesic) with cannabinoids and opioids [8]

Considering the potential role of the imidazoline receptor in the pharmacology of psychoactive substances - some showing notable affinity [see here, or for the β-carbolines here], one could explore the hypothesis that it may be an interesting approach for augmenting the therapeutic effects of multiple substances.

For further information, see: Imidazoline binding sites on receptors and enzymes: Emerging targets for novel antidepressant drugs?

With agmatine being a readily available supplement, one may wish to cautiously experiment :)

If anyone has anything to add, please feel free to do so.

Edited by Alchemica
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