Effect of SUN C5174, a novel 5-HT_2 receptor antagonist, on various experimental models of peripheral circulatory disturbance

• Published in: Japanese Journal of Pharmacology 1999, Vol.79 (suppl.1), p.193-193
• Main Authors: Atsuto Ogata, Yoshiyuki Kamiide, Hiromitu Takagi, Satomi Mekata, Yoshiko Horikawa, Akira Mizuno, Norio Inomata
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

SUN C5174 is a novel 5-HT_2 receptor antagonist with a mild α_1 -adrenergic action. In this study, we investigated the effectiveness of SUN C5174 on peripheral circulatory disturbance using various experimental animal models. In a mouse model of acute pulmonary thrombotic death induced by simultaneous injection of serotonin and collagen, SUN C5174 significantly inhibited the mortality rate at an oral dose of 0.3 mg/kg. In a rat model of tail occlusion induced by carrageenin, SUN C5174 (10 mg/kg, p.o.) improved caudal disorder. In a model of tail gangrene induced by epinephrine and ergotamine, SUN C5174 (1 mg/kg, p.o.) improved caudal disorder. In a rabbit model of thrombosis induced by femoral arterial electric simulation, SUN C5174 (0.01 mg/kg, i.v.) prolonged time to thrombosis. In a serotonin induced waking impairment model of femoral artery ligated rat, SUN C5174 (0.03 mg/kg, p.o.) prolonged waking time. In a collagen induced reduction of calf muscle constrictive tension (fatigue) model of femoral artery ligated rat, SUN C5174 (3 mg/kg, p.o.) improved fatigue and limb blood flow. Moreover in these various experimental models of peripheral circulatory disturbance, SUN C5174 improved the disorder at lower doses compared with sarpogrelate, cilostazol and ticlopidine. These results indicate that SUN C5174 has the therapeutic potential against peripheral circulatory disturbance.