Long-acting 5-HT2A antagonist
AT 1015 is a potent antagonist of 5-HT2A receptor [1].
The 5-HT2A receptor is a G protein-coupled receptor and a subtype of the 5-HT2 receptor, which belongs to the serotonin receptor family. The 5-HT2A receptor plays an important role in clathrin mediated endocytosis of JC virus, the human polyoma virus which causes progressive multifocal leukoencephalopathy (PML).
AT 1015 is a potent 5-HT2A receptor antagonist. AT 1015 bound to 5-HT2 receptors in rabbit cerebral cortex membrane with pKi value of 7.94 [1].
In a photochemically induced rat femoral arterial thrombosis (PIT) model, AT 1015 (1 mg/kg) significantly inhibited vascular contraction induced by 5-HT and prolonged the time for 24 h that required to occlusion of the artery in a dose-dependent way. While, AT 1015 (10 mg/kg) didn’t prolong bleeding time in the tail transection bleeding time test [2]. AT 1015 inhibited 5-HT2A receptor-mediated platelet aggregation both in vitro and in rat. In the rat peripheral vascular lesion model, AT 1015 (1 mg/kg) significantly inhibited progression of peripheral vascular lesions [3].
参考文献:
[1].? Rashid M, Watanabe M, Nakazawa M, et al. Assessment of affinity and dissociation ability of a newly synthesized 5-HT2 antagonist, AT-1015: comparison with other 5-HT2 antagonists. Jpn J Pharmacol, 2001, 87(3): 189-194.
[2].? Kihara H, Koganei H, Hirose K, et al. Antithrombotic activity of AT-1015, a potent 5-HT(2A) receptor antagonist, in rat arterial thrombosis model and its effect on bleeding time. Eur J Pharmacol, 2001, 433(2-3): 157-162.
[3].? Kihara H, Hirose K, Koganei H, et al. AT-1015, a novel serotonin (5-HT)2 receptor antagonist, blocks vascular and platelet 5-HT2A receptors and prevents the laurate-induced peripheral vascular lesion in rats. J Cardiovasc Pharmacol, 2000, 35(4): 523-530.
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