Antidepressants glutamate receptors

Eollowing chronic administration to rats, there is evidence that most antidepressants cause adaptive changes in S-HT a/ 5-HT2a alpha-1, alpha-2 and beta adrenoceptors, GABA-B receptors and possibly the NMDA-glutamate receptors. 

In experimental studies, chronic antidepressant treatments have been shown to reduce the behavioural effects of the NMDA-glutamate receptor antagonist dizolcipine. This suggests that antidepressants may act as functional NMDA receptor antagonists and thereby reduce excitatory glutamate transmission which is mediated by NMDA receptors. 

Chaki S, Yoshikawa R, Hirota S, et al (2004) MGS0039 a potent and selective group II metabotropic glutamate receptor antagonist with antidepressant-like activity. Neuropharmacology 46 457-467... 

Since the early 1990s evidence has accumulated to show that a variety of drugs that block the glutamate receptor of the NMDA subtype have antidepressant-like profiles in behavioral... 

Palucha A, Pile A (2007) Metabotropic glutamate receptor ligands as possible anxiolytic and antidepressant drugs. Pharmacol Ther 115 116-147... 

Skolnick P. Modulation of glutamate receptors strategies for the development of novel antidepressants. Amino Acids 2002 23 153-159. 

Mitani H, Shirayama Y, Yamada T, Maeda K, Ashby CR, Kawa-hara R. Correlation between plasma levels of glutamate, alanine, and serine with severity of depression. Progr. Neuro-Psycho-pharmacol. Biol. Psychiatry 2006 30 1155-1158. Martinez-Turrillas R, Erechilla D, Del Rio J. Chronic antidepressant treatment increases the membrane expression of AMPA receptors in rat hippocampus. Neuropharmacology 2002 43 1230-1237. Petty E. GABA and mood disorders a brief review and hypothesis. J. Affec. Disorders 1995 34 275-281. 

Carbamazepine is both an important anticonvulsant in therapeutic doses and a powerful proconvulsant in overdose. The therapeutic anticonvulsant mechanism is primarily related to blockade of presynaptic voltage-gated sodium channels. Blockade of the sodium channels is believed to inhibit the release of synaptic glutamate and possibly other neurotransmitters. Carbamazepine is also a powerful inhibitor of the muscurinic and nicotinic acetylcholine receptors, N-methyl-D-aspartate (NMDA) receptors and the central nervous system (CNS) adenosine receptors. In addition, carbamazepine is structurally related to the cyclic antidepressant impramine and in massive overdose may affect cardiac sodium channels. 

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