Pharmacological evaluation of the histamine H1 and 5-HT blocking properties of 2-N-(carboxamidinonormianserin) (FCC5): in-vitro studies.
Some in-vitro pharmacological effects of a novel analogue of mianserin, 2-carboxamidino-1,2,3,4,10,14b-hexahydrodibenzo (c,f) pyrazino (1,2-alpha) azepine hydrochloride (FCC5) have been studied. FCC5 was a non-competitive antagonist of both histamine-induced contractions of the guinea-pig ileum and 5-HT-induced contractions of rat fundal strips with pD'2 values of 6.13 and 5.57, respectively. The insurmountable antihistaminic effect of FCC5, 100 nM, in the guinea-pig isolated ileum was not removed by washing. FCC5, 10-100 nM, had no effect on responses to acetylcholine or barium chloride of the guinea-pig isolated ileum. In guinea-pig isolated right atria, FCC5, 1-30 microM, had no effect on H2-receptor-mediated chronotropic responses to histamine. FCC5, 10-1000 nM, had no alpha 2-adrenoceptor antagonist activity, as assessed by lack of effect on the inhibitory responses to B-HT 920 in the electrically stimulated rat isolated vas deferens. FCC5 resembles mianserin by being a potent, non-competitive antagonist at histamine H1 and 5-HT receptors, but differs from mianserin in a number of respects including having much less effect at alpha 2-adrenoceptors.
Leitch
I M
IM
Department of Pharmacology, Monash University, Victoria, Australia.
Boura
A L
AL
King
R G
RG
D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011738:Pyrilamine / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects
D006634:Histamine H1 Antagonists; D012702:Serotonin Antagonists; C075499:2-N-carboxamidinonormianserin; D008803:Mianserin; D006632:Histamine; D011899:Ranitidine; D011738:Pyrilamine