Binding of the putative anxiolytic TVX Q 7821 to hippocampal 5-hydroxytryptamine (5-HT) recognition sites.
The abilities of the putative non-benzodiazepine anxiolytic compound TVX Q 7821 in comparison to 5-HT and the 5-HT2 receptor antagonist ketanserin to displace 3H-5-HT from its binding sites in various regions of calf brain were studied. Binding affinities and capacities for 3H-5-HT were determined using membranes from different calf brain regions. Competition experiments with radiolabelled 3H-ketanserin using rat prefrontal cortex membranes were also performed. High affinity 3H-5-HT binding was found in all calf brain areas examined, with the hippocampus having the highest density of binding sites. TVX Q 7821 was a potent displacer (Ki-value 10 nmol/l) of 3H-5-HT binding in hippocampal membranes but not in membranes from other brain regions. No high affinity binding of TVX Q 7821 was found to the 5-HT receptors labelled with 3H-ketanserin. It is concluded, that TVX Q 7821 may bind preferentially to a special subtype of the 5-HT1 recognition site. Furthermore the results suggest that these sites may be involved in the mechanism of the anxiolytic action of TVX Q 7821.
Glaser
T
T
Traber
J
J
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D006624:Hippocampus / Q000378:metabolism*; D007650:Ketanserin; D007700:Kinetics; D008566:Membranes / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism*; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*
D010880:Piperidines; D011743:Pyrimidines; D011985:Receptors, Serotonin; C043077:ipsapirone; D007650:Ketanserin