5-hydroxytryptamine antagonistic effects of ICI 169,369, ICI 170,809 and methysergide in human temporal and cerebral arteries.
ICI 169,369 and ICI 170,809 are two chemically novel 5-HT antagonists that have high affinity for the 5-HT2 binding site in rat cortex (Ki 1.79 x 10(-8)M and 6.6 x 10(-10)M, respectively). In human temporal artery preparations ICI 169,369 was shown to cause a progressive rightward shift of the 5-HT-response curve over the range 10(-7)-10(-5)M, while ICI 170,809 in these concentrations shifted the curve to the same degree (no dose dependency). In human cerebral vessels no effect was observed until a high concentration (10(-5)M) was used for either compounds. The mixed 5-HT1/5-HT2 antagonist, methysergide, induced a non parallel rightward shift of the 5-HT-induced concentration-effect curve with a depression of the maximum achievable response in both the temporal and cerebral artery. The mode of effect of ICI 169,369 and ICI 170,809 to block the 5-HT-induced contractions in human temporal vessels resembles that of the pure 5-HT2 antagonist ketanserin, thus suggesting that the two ICI compounds are mainly 5-HT2 antagonists. In high concentrations both ICI 169,369 and ICI 170,809 have vasorelaxant properties, explaining the reduction in maximum 5-HT-induced contraction seen at high antagonist concentrations.
Jansen
I
I
Department of Experimental Research, University of Lund, Malmö General Hospital, Sweden.
Blackburn
T
T
Eriksen
K
K
Edvinsson
L
L
D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008784:Methysergide / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011804:Quinolines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013699:Temporal Arteries / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D011804:Quinolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C054363:2-((2-(dimethylamino)ethyl)thio)-3-phenylquinoline; C060632:ICI 170809; D008784:Methysergide