RS-127445 is a selective, high affinity 5-HT2B receptor antagonist.
The 5-HT2B receptor is a G-protein coupled receptor. 5-HT2B receptors are widely expressed in peripheral tissues of various species. 5-HT2B receptor expresses throughout the gastrointestinal tract including smooth muscle of the stomach fundus, oesophagus, colon and small intestine. The receptor has also been found in the placenta, uterus, lung and prostate. 5-HT2B receptors are present in many vascular beds and have been localized to both vascular smooth muscle and vascular endothelial cells [1].
RS-127445 (2-amino-4-(4-fluoronaphth-1-yl)-6-isopropylpyrimidine) showed nanomolar affinity for the 5-HT2B receptor with the pKi of 9.5 ± 0.1. In cells expressing human recombinant 5-HT2B receptors, RS-127445 potently antagonized 5-HT-evoked formation of inositol phosphates (pKB = 9.5 ± 0.1) and 5-HT-evoked increases in intracellular calcium (pIC50 = 10.4 ± 0.1). RS-127445 blocked 5-HT-evoked contraction of rat isolated stomach fundus (pA2 = 9.5 ± 1.1) and (±)α-methyl-5-HT-mediated relaxation of the rat jugular vein (pA2 = 9.9 ± 0.3). In rats, RS-127445 was bioavailable via the oral or intraperitoneal routes.
Reference:
[1] Bonhaus D W, Flippin L A, Greenhouse R J, et al. RS‐127445: a selective, high affinity, orally bioavailable 5‐HT2B receptor antagonist[J]. British journal of pharmacology, 1999, 127(5): 1075-1082.
