Marlene L. Cohen, W. Colbert, Laura A. Wittenauer
Drug Development Research
LY53857 is a potent antagonist at vascular 5HT2 receptors that lacks prominent α1 or dopamine antagonist activity. The present report investigates the interaction of LY53857 with other receptor mechanisms. LY53857 showed no agonist activity in the guinea pig trachea, guinea pig atria, guinea pig ileum, or rat vas deferens. Furthermore, LY53857 did not antagonize histamine (H1) or β2 receptors in the guinea pig trachea, β1 in the guinea pig atria, muscarinic, or angiotensin I receptors in the guinea pig ileum. However, LY53857 did block α2 receptors (−log KB = 6.51) as determined by antagonism of the inhibitory effects of the selective β2 agonist, UK‐14,304, on the twitch response in the guinea pig ileum. LY53857 antagonized β2 receptors at concentrations approximately 6000‐fold higher than necessary to block 5HT2 receptors (−log KB = 10.3). Taken in concert, these data support the contention that LY53857 is a highly selective antagonist of 5HT2 receptors, and that LY53857 is a useful tool with which to probe 5HT2 receptors and serotonergic mechanisms.