In vitro studies with ICI 169,369, a chemically novel 5-HT antagonist.

ICI 169,369 is a chemically novel 5-HT antagonist that has higher affinity for the 5-HT2 binding sites in rat cortex than it has for 5-HT1 sites (Ki 1.79 x 10(-8) and 1.58 x 10(-6) M, respectively). In isolated tissue preparations ICI 169,369 was shown to be a competitive antagonist of 5-HT on the rabbit aorta, pig coronary artery and rat caudal artery. In the latter preparation it had a similar pA2 value to ketanserin (pA2 8.18 +/- 0.5 and 8.42 +/- 0.06, respectively). Unlike ketanserin, which was inactive, ICI 169,369 was a non-surmountable antagonist at the rat stomach fundus 5-HT 'D' receptor, recently reclassified as 5-HTIC. It was inactive (greater than 10(-6) M) at the 5-HT3 receptors found in the isolated perfused rabbit heart and the myenteric plexus of the guinea-pig ileum. At receptors other than those for 5-HT (alpha 1, alpha 2, beta 1, beta 2, H1, H2 and muscarinic), ICI 169,369 was inactive at concentrations of either 10(-6) or 10(-5) M. Thus the profile of ICI 169,369 should make it useful in the analysis of the role of 5-HT in physiological and pathological states.