Cohen M L, Johnson M P, Schenck K W, Susemichel A, Wainscott D B, Robertson D W, Nelson D L
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana.
J Pharmacol Exp Ther. 1993 Aug;266(2):943-9.
Both alpha-methylserotonin and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) are agonists at 5-hydroxytryptamine2 (5-HT2) receptors. The present study compared these agonists for their binding affinities at the high- and low-affinity states of the 5-HT2 receptor and for their contractile activities in certain smooth muscle preparations. Both agonists contracted the rat aorta and rat jugular vein, tissues possessing 5-HT2 receptors, and contraction was blocked by ketanserin. However, alpha-methylserotonin produced greater maximal response (80-90% maximum response to serotonin) than DOI. In the rat jugular vein, the calculated dissociation constant of DOI (-log Kb = 7.7) corresponded well with its affinity for [3H]ketanserin- (pKi = 7.5) but not [125I]DOI- (pKi = 8.6) radiolabeled sites. This might suggest that binding to the agonist low-affinity state of the 5-HT2 receptor is more relevant to vascular agonist activity. alpha-Methylserotonin was slightly more potent than serotonin in contracting the rat aorta but not the jugular vein, whereas DOI was more potent in the jugular vein than in the aorta. In the jugular vein but not the aorta, the relative potency of these agents corresponded well with their relative affinities for either the [3H]ketanserin- or the [125I]DOI-labeled 5-HT2 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
