Pharmacological profile of neuroleptics at human monoamine transporters

Using radioligand binding techniques, we determined the equilibrium dissoci ation constants (K-D) for 37 neuroleptics and one metabolite of a neurolept ic (haloperidol metabolite) for the human serotonin, norepinephrine, and do pamine transporters with [H-3]imipramine, [H-3]nisoxetine, and [H-3]WIN3542 8, respectively. Among neuroleptics, the four most potent compounds at the human serotonin transporter were triflupromazine, fluperlapine, chlorpromaz ine, and ziprasidone (K-D 24-39 nM); and at the norepinephrine transporter, chlorpromazine, zotepine, chlorprothixene, and promazine (K-D 19-25 nM). A t the human dopamine transporter, only pimozide (K-D = 69 +/- 3) ziprasidon e (K-D = 76 +/- 5) had notable potency. These data may be useful in predict ing therapeutic and adverse effects, including drug interactions of neurole ptics. (C) 1999 Elsevier Science B.V. All rights reserved.