5-Hydroxytryptamine (5-HT, also commonly known as serotonin) is synthesized in enterochromaffin cells in the intestine and in serotonergic nerve terminals. In the periphery, 5-HT mediates gastrointestinal motility, platelet aggregation, and contraction of blood vessels. Many functions of the central nervous system are influenced by 5-HT, including sleep, motor activity, sensory perception, arousal and appetite. A family of 12 GPCRs and one ion channel mediate the biological effects of 5-HT (Hoyer et al., 1994). The 5-HT2B receptor, which couples to Gq/11 to increase intracellular calcium, is expressed in embryonic and adult cardiovascular tissues, gut and brain from the rat, mouse, and human species. A role for 5-HT2B receptors was suggested in the cardiopathy associated with fenfluramine (Fitzgerald et al., 2000). Cloned human 5-HT2B expressing cell line is made in the CHO host, which supports high levels of recombinant 5-HT2B expression on the cell surface for functional detection via the calcium signaling pathway. Thus, the cell line is an ideal tool for screening for agonists, antagonists and modulators at 5-HT2B.