No evidence for functional involvement of 5-HT2B receptors in serotonin-induced vasodilatation in the human forearm

The receptor involved in the serotonin (5-hydroxytryptamine [5-HT])-induced vasodilatation in the human forearm has not yet been identified. Experimen tal data point to the 5-HT2B receptor located on the endothelium. RS-127445 (2-amino-4-(4-fluoronaphthyl-1-yl)-6-isopropylpyrimidine) is a novel poten t and selective 5-HT2B receptor antagonist. The effect of oral RS-127445 (5 00 mg) on 5-HT-induced vasodilatation was studied in a double-blind, random ized, placebo-controlled, crossover study in six healthy volunteers. On eac h study day 5-HT (0.5 ng/kg/min) was infused into the brachial artery for 8 min, before drug administration and at intervals of 20, 65, 110, 230, and 470 min after oral ingestion. At each infusion, plasma samples for study dr ug assay were taken and forearm blood flow was assessed using venous occlus ion plethysmography. Although (log) drug concentrations exceeded pKi, there was no correlation between RS-127445 concentrations and 5-HT-induced vasod ilatation. 5-HT-induced vasodilatation did not differ between treatments an d time points. It appears that there is no functional involvement of 5-HT2B receptors in 5-HT-mediated vasodilatation in the human forearm.