Central dopaminergic and 5-hydroxytryptaminergic effects of C(3)-methylated derivatives of 8-hydroxy-2-(di-n-propylamino)tetralin
- 1 June 1988
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 31 (6) , 1130-1140
- https://doi.org/10.1021/jm00401a012
Abstract
A number of stereochemically well defined C3-methylated derivatives of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) have been synthesized, and their stereochemical characteristics have been studied by use of NMR spectroscopy, X-ray crystallography, and molecular mechanics calculations. The compounds were tested for activity at central 5-HT and dopamine (DA) receptors, by use of biochemical and behavioral tests in rats. In addition, the ability of the cis- and trans-8-hydroxy-3-methyl-2-(di-n-propylamino)tetralins (15 and 11) to displace [3H]-8-OH-DPAT from 5-HT1A binding sites was evaluated. The stereoselectivity of the interaction of 11 and 15 with 5-HT receptors was much greater than that of 8-OH-DPAT. Observed rank order of potencies in the 5-HT1A binding assay corresponds to that in the in vivo biochemical assay.This publication has 22 references indexed in Scilit:
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