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Newsgroups: alt.psychoactives
From: (William E. White )
Subject: There is a specific beta-carboline binding site!
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).