The selective labelling of central 5-HT1A receptor binding sites by [3H]5-methoxy-3-(di-n-propylamino)chroman.
Investigations on the pharmacological properties of a series of chroman derivatives indicated that 5-methoxy-3-(di-n-propylamino)chroman (5-MeO-DPAC) acts in the nM range on 5-HT1A sites but recognizes very poorly other 5-HT sites and D2 sites in rat brain membranes. As expected from these observations, the tritiated derivative [3H]5-MeO-DPAC bound to a single class of specific sites which exhibited the same pharmacological properties as 5-HT1A sites labelled by [3H]8-OH-DPAT in hippocampal and cortical membranes. In contrast to [3H]8-OH-DPAT, [3H]5-MeO-DPAC did not bind to presynaptic striatal sites (possibly associated with 5-HT reuptake in serotoninergic terminals), which indicated that this new chroman derivative was even more selective than the [3H]tetralin ligand for the in vitro labelling of 5-HT1A sites. Comparison of the chemical structures of 5-MeO-DPAC and other 5-HT1A ligands suggests that electronic enrichment due to isosteric O-substitution in the chroman derivative may play an important role in the highly selective recognition of the 5-HT1A receptor by this drug.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001578:Benzopyrans; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000187:drug effects; D002839:Chromans / Q000138:chemical synthesis / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013764:Tetrahydronaphthalenes
D001578:Benzopyrans; D002839:Chromans; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C054083:5-methoxy-3-(di-n-propylamino)chroman; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin