High-affinity, 5-HT2B subtype-selective serotonin receptor antagonist with in vitro and in vivo efficacy.
LY272015 is a high-affinity, 5-HT2B subtype-selective serotonin receptor antagonist (5-HT2B -log KB = 9.86, 5-HT2A/5-HT2C -log Ki = 7.65/7.92) that exhibits antihypertensive efficacy in deoxycorticosterone acetate (DOCA)-salt-hypertensive rats in vivo (1, 3 mg/kg iv; 1x/wk for 4 wks). LY272015 inhibits mitral valve interstitial cell (MVIC) activation by 5HT in cultures (100 nM LY, 10 nM or 1 μM 5HT; canine MVIC) and ex vivo (100 μM LY, 10 μM 5HT; human MV), as well as mitigates angiotensin II infusion-provoked MV remodeling in mice in vivo (3 mg/kg via infusion by osmotic pumps 2x/wk).
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