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Receptor specificity of the 5HT 2 receptor antagonist, LY53857
Author(s) -
Cohen Marlene L.,
Colbert Walter,
Wittenauer Laura A.
Publication year - 1985
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430050404
Subject(s) - receptor , agonist , competitive antagonist , 5 ht receptor , guinea pig , medicine , endocrinology , antagonist , receptor antagonist , pharmacology , serotonin , histamine , chemistry , muscarinic acetylcholine receptor , ileum , biology
LY53857 is a potent antagonist at vascular 5HT 2 receptors that lacks prominent α 1 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 (H 1 ) or β 2 receptors in the guinea pig trachea, β 1 in the guinea pig atria, muscarinic, or angiotensin I receptors in the guinea pig ileum. However, LY53857 did block α 2 receptors (−log K B = 6.51) as determined by antagonism of the inhibitory effects of the selective β 2 agonist, UK‐14,304, on the twitch response in the guinea pig ileum. LY53857 antagonized β 2 receptors at concentrations approximately 6000‐fold higher than necessary to block 5HT 2 receptors (−log K B = 10.3). Taken in concert, these data support the contention that LY53857 is a highly selective antagonist of 5HT 2 receptors, and that LY53857 is a useful tool with which to probe 5HT 2 receptors and serotonergic mechanisms.