Inhibitory effects of AT-1015. newly synthesized 5-HT_2A receptor antagonist, on contraction of porcine coronary arteries induced by 5-HT

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.1), p.183-183
• Main Authors: Haibin Gong, Mamunur Rashid, Takashi Nakamura, Kaoru Hattori, Toshio Ohnuki, Mikio Nakazawa, Hideaki Kihara, Ryota Yoshimoto, Takafumi Nagatomo
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Inhibitory effects of a newly synthesized 5-HT_2A receptor antagonist, AT-1015 on contraction of porcine coronary arteries mediated 5-HT_2A receptor subtypes was evaluated and this result compared with that of ketanserin and sarpogrelate. The endothelium was denuded mechanically by gentle abrasion of the luminal surface with tissue forceps and its absence was demonstrated by failure of the strips contracted by acetylcholine (10^6 M). The contraction was determined by adding 5-HT or α-methylserotonine (α-Me-5-HT) as agonists. Ketanserin and sarpogrelate caused rightward shifts of contraction by dose-dependent manners of two agonists. On the other hand, AT-1015 reduced maximal both 5-HT and α-Me-5-HT-induced contraction and caused rightward shifts of contraction by dose-dependent manners of the two agonists and pK_B values of AT-1015 were 9.04±0.11 (5-HT) or 8.61±0.11, respectively. The rank order of pK_B values of three antagonists were AT-1015 > ketanserin > sarpogrelate (5-HT) and ketanserin ≧ AT-1015 > sarpogrelate (α-Me-5-HT), respectively. Thus, these results suggest that AT-1015 is a strong 5HT_2A antagonist to porcine coronary arteries and that this drug exhibited different pharmacological profiles in the coronary arteries from those of ketanserin and sarpogrelate.