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.
Blackburn
T P
TP
ICI Pharmaceuticals Division, Research Department II, Macclesfield, Cheshire, U.K.
Thornber
C W
CW
Pearce
R J
RJ
Cox
B
B
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013045:Species Specificity; D013552:Swine
D011804:Quinolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline; D008729:Methoxamine