TY - JOUR T1 - Determination of selective and nonselective compounds for the 5-HT 1A and 5-HT 1B receptor subtypes in rat frontal cortex. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 480 LP - 487 VL - 231 IS - 3 AU - M A Sills AU - B B Wolfe AU - A Frazer Y1 - 1984/12/01 UR - http://jpet.aspetjournals.org/content/231/3/480.abstract N2 - 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) ER -