Inhibition of diazepam binding by tryptophan derivatives including melatonin and its brain metabolite N-acetyl-5-methoxy kynurenamine

P. J. Marangos, J. Patel, F. Hirata, D. Sondhein, S. M. Paul, P. Skolnick, F. K. Goodwin

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

The presence of specific binding sites for the benzodiazepines in brain has generated the hypothesis that an endogenous ligand for this receptor exists. In the present report a series of tryptophan derivatives were tested for their ability to inhibit [3H] diazepam binding to rat brain synaptosomal membranes. Of the derivatives tested melatonin and its brain metabolite N-acetyl 5-methoxy kynurenamine (AMK) were found to be the most potent. Melatonin and AMK display respective Ki values for the inhibition of diazepam binding of 415 μM and 49 μM. Melatonin is therefore twice as potent as inosine or hypoxanthine and AMK about 20-fold more potent. Both compounds display competitive inhibition kinetics and do not inhibit binding of a variety of other neurotransmitters to their respective receptors. The data suggest that these or similar agents may serve as endogenous modulators of the benzodiazepine receptor.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalLife Sciences
Volume29
Issue number3
DOIs
StatePublished - Jul 20 1981
Externally publishedYes

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