Newsgroups: alt.psychoactives From: firstname.lastname@example.org (William E. White ) Subject: There is a specific beta-carboline binding site! Message-ID:
Date: Mon, 14 Nov 1994 16:16:00 GMT While going through journals this weekend I came across an interesting study which (although not, to my knowledge replicated yet, seems to have OK methodology) has found a specific binding site for norharman (beta-carboline). This is fairly old so maybe it's been refuted (or maybe everyone but me knows this already). In particular this was before the explosion of identified 5HT receptor types (which now includes 5HT1A, 5HT1B, 5HT1C, 5HT1Dalpha, 5HT1Dbeta, 5HT1E, 5HT1F, 5HT2, 5HT3, 5HT4, 5HT5A, 5HT5B, 5HT6, and 5HT7!) The abstract: Journal of Chemical Neuroanatomy 1990 Jan-Feb;3(1):19-24 "Quantitative autoradiography of [3H]norharman ([3H]beta-carboline) binding sites in the rat brain." The anatomical distribution of [3H]norharman binding sites was determined by quantitative autoradiography in rat brain slices. They are enriched in hypothalamic, thalamic, accumbens and amygdaloid nuceli as well as in hippocampal, neocortical, and olfactory-related structures. The distri- bution pattern differs from that of other previously described receptors or binding sites (e.g., monoamine oxidase, benzodiazepine, tryptamine, 5-hydroxytryptamine receptors (5-HT1a, 5-HT1B, 5-HT1C, 5-HT2), which suggests that a unique class of [3H]norharman binding sites exists in the rat brain. The findings are consistent with previous experiments which showed high-affinity binding sites for [3H]norharman in rat brain membranes (KD 1.552 nM; autoradiography KD 5.5nM). A correspondance in the displacing activity of drugs was found for both methods (crude membrane fraction: harman much greater than tryptamine much greater than 5-hydroxytryptamine greater than N-methyl-beta-carboline-3-carboxamide (FG 7142) = diazepam; autoradiography: harman much greater than tryptamine much greater than FG7142 greater than 5-hydroxytryptamine greater than diazepam). Provided that the binding sites represent functional receptors, the present anatomical findings may explain the biological effects of norharman, e.g. pro-conflict behaviour (limbic-hypothalamic structures), tonic-clonic convulsions (limbic-cortical structures) and alterations of locomotor activity (accumbens nucleus).