5-HT-1a and 5-HT-1b selectivity of two phenylpiperazine derivatives: evidence for 5-HT-1b heterogeneity.
The ability of m-trifluoromethylphenylpiperazine (TFMPP) and an N-substituted derivative, LY 165163 (p-NH2-PE-TFMPP), to discriminate 5-HT-1 binding sites labelled by [3H]5-HT is compared in rat corpus striatum and rat cortex. TFMPP displays at least a 30 fold selectivity for the 5-HT-1b subtype. Furthermore, TFMPP reveals heterogeneity within the 5-HT-1b binding sites. TFMPP displays a Kd of 6 nM for approximately two-thirds of the 5-HT-1b binding sites and a Kd of 273 nM for the remaining one third of the 5-HT-1b sites. p-NH2-PE-TFMPP, on the other hand, discriminates the 5-HT-1 sites in a manner similar to spiperone, displaying a 110 fold selectivity for the 5-HT-1a sites. p-NH2-PE-TFMPP displays a Kd of about 3 nM for the 5-HT-1a sites. p-NH2-PE-TFMPP does not discriminate subtypes within the 5-HT-1b binding sites. The significance of the selectivity of these two compounds as well as structurally related compounds is discussed.
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism
D010879:Piperazines; D011985:Receptors, Serotonin; C018406:1-(3-trifluoromethylphenyl)piperazine; D013134:Spiperone; C044643:LY 165163