Determination of selective and nonselective compounds for the 5-HT 1A and 5-HT 1B receptor subtypes in rat frontal cortex.
Recent studies indicate that there are multiple subtypes of the 5-hydroxytryptamine 1 (5-HT1) receptor. Previously, we provided evidence consistent with the finding that multiple states of the 5-HT1 receptor are present when the binding of [3H]-5-HT is measured in the absence of guanine nucleotides. When 1 mM GTP was present in the [3H]-5-HT receptor binding assay, the high affinity state was eliminated. As the presence of multiple states of a receptor complicates the interpretation of the inhibition of [3H]-5-HT binding caused by serotonin agonists and antagonists, we examined the ability of a series of these drugs to compete for 15 nM [3H]-5-HT binding in the presence of 1 mM GTP in the rat frontal cortex. Eight agonists and five antagonists showed selectivity for the two subtypes of the 5-HT1 receptor, whereas three agonists and four antagonists showed the same affinity for these two receptors subtypes. Most of the compounds examined exhibited only a modest 10- to 30-fold degree of selectivity. However, 1-(m-trifluoromethylphenyl) piperazine and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)indole were about 65-fold selective and spiperone was over 100-fold selective for one of the receptor subtypes. The subtype specificity of the selective compounds was determined using either spiperone, a selective 5-HT 1A compound, or 1-(m-trifluoromethylphenyl)piperazine, a selective 5-HT 1B compound, to preferentially inhibit one of the receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001667:Binding, Competitive; D005625:Frontal Lobe / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000378:metabolism
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D006160:Guanosine Triphosphate