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

doi:10.1016/0024-3205(81)90242-3

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

Washington University School of Medicine

Research output: Contribution to journal › Article › peer-review

83 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 K_i 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 language	English
Pages (from-to)	259-267
Number of pages	9
Journal	Life Sciences
Volume	29
Issue number	3
DOIs	https://doi.org/10.1016/0024-3205(81)90242-3
State	Published - Jul 20 1981

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

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.",

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T1 - Inhibition of diazepam binding by tryptophan derivatives including melatonin and its brain metabolite N-acetyl-5-methoxy kynurenamine

AU - Marangos, P. J.

AU - Patel, J.

AU - Hirata, F.

AU - Sondhein, D.

AU - Paul, S. M.

AU - Skolnick, P.

AU - Goodwin, F. K.

PY - 1981/7/20

Y1 - 1981/7/20

N2 - 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.

AB - 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.

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

Abstract

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