 In 2008, AMG 517, a highly selective TRPV1 antagonist was dropped out of clinical trials due to the causation of hyperthermia (~38.3oC mean increase which was most intense on day 1 but was attenuated on days 2-7.A second molecule, SB-705498, was also evaluated in the clinic but its effect on body temperature was not reported.As we increase understanding of modality specific agonism of TRPV1 it seems that next generation therapeutics targeting TRPV1 have the potential to side-step hyperthermia.