Drug actions of serotonin uptake inhibitors were first compared in human and bovine serotonin transporter (SERT) transfected in COS-1 cells. Uptake of tritiated serotonin was used to measure uptake after applying a variety of serotonergic drugs to cells either containing human or bovine SERT. Human SERT (hSERT) was more strongly affected by the SSRIs citalopram, fluoxetine, and paroxetine, and by the tricyclic antidepressant imipramine than bovine SERT (bSERT). No species-specific differences were found between hSERT and bSERT for the SSRIs fluvoxamine and sertraline, for the psychostimulants cocaine and Beta-carbo-methoxy-3beta-4(iodophenyl)tropane or for MDMA. MDMA potencies, determined in uptake inhibition studies and reported as IC50, was 819 +/- 90 for hSERT and 903 +/- 178 for bSERT. Transporters combining specific elements of human and bovine SERT structure were used to examine the structural differences in hSERT and bSERT causing differential sensitivity to some SSRIs; these studies did not use MDMA as a test drug. It would appear that the pharmacokinetic actions between MDMA and the serotonin transporter are conserved at least across mammals, meaning that most mammals possess serotonin transporters that will be sensitive to MDMA.