Inhibitory effects of a newly synthesized 5-HT2 receptor antagonist, AT-1015 (N-[2-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidino]-ethyl]-1-for myl-4-piperidinecarboxamide monohydrochloride monohydrate), on contraction and relaxation of pig coronary arteries induced by 5-HT and alpha-methylserotonin: comparison with ketanserin.
Inhibitory effects of a newly synthesized 5-HT2 receptor antagonist, AT-1015 (N-[2-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidinolethyl ]-1-formyl-4-piperidinecarboxamide monohydrochloride monohydrate) on contraction and relaxation of coronary arteries of pig hearts mediated by 5-HT2 subtypes were evaluated and these results were compared with those of ketanserin. Contraction and relaxation were determined by adding 5-HT or alpha-methylserotonin (alpha-Me-5-HT) as agonists. Although ketanserin induced rightward shifts of contraction, AT-1015 inhibited the maximal response. In addition, ketanserin inhibited relaxation induced by high concentration of agonists, but there were no inhibitory effects of AT-1015 on relaxation. Thus, these results suggest that AT-1015 is a strong non-competitive 5-HT2 antagonist in porcine coronary arteries and that this drug clearly exhibited different effects on the contraction and relaxation of coronary arteries of pig hearts from those of ketanserin.
Gong
H
H
Department of Pharmacology, Niigata College of Pharmacy, Japan.
Rashid
M
M
Nakamura
T
T
Hattori
K
K
Nakazawa
M
M
Kihara
H
H
Yoshimoto
R
R
Nagatomo
T
T
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007540:Isonipecotic Acids / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D007540:Isonipecotic Acids; C411870:N-(2-(4-(5H-dibenzo(a,d)cyclohepten-5-yliden)piperidino)ethyl)-1-formyl-4-piperidinecarboxamide; D012702:Serotonin Antagonists; C042390:alpha-methylserotonin; D012701:Serotonin; D007650:Ketanserin