5-Hydroxytryptamine receptor in isolated rabbit aorta: Characterization with tryptamine analogs

The 5-HT₂ receptor in isolated rabbit thoracic aorta was characterized by examining the relationships between structure and activity of nine tryptamine analogs. All assays were conducted after blockade of the alpha adrenergic receptor and inactivation of the neuronal uptake-1 system and monoamine oxidase. Seven of the analogs tested were agonists. 6-Hydroxytryptamine and 7-hydroxytryptamine showed little or no agonist activity in this preparation. The pA₂ of spiperone was independent of the agonist assayed and defined the receptor activated by each agonist as the 5-HT₂ receptor. The dissociation constant (K(A)) and relative intrinsic efficacy were determined for each agonist. The K(A) and relative intrinsic efficacy values for 5-hydroxytryptamine were 0.25 μM and 1, respectively. The K(A) and relative intrinsic efficacy values for 5-methoxytryptamine were 0.14 μM and 0.86, respectively, and were not significantly different from those for 5-hydroxytryptamine. The other five analogs were partial agonists. N-Methyl-5-hydroxytryptamine and bufotenine had relative intrinsic efficacies of about 0.3 and K(A) values not statistically different from the K(A) value for 5-hydroxytryptamine. Tryptamine, 5-methyltryptamine and alpha-methyl-tryptamine had K(A) values of about 1 μM and relative intrinsic efficacies of 0.6, 0.6 and 0.4, respectively. These results revealed the differential effects of structural changes on drug affinity and intrinsic efficacy. This information will be applicable in the design of selective agonists of antagonists for the classification of less well defined 5-hydroxytryptamine receptors.