Pharmacological profile of neuroleptics at human monoamine transporters.
Using radioligand binding techniques, we determined the equilibrium dissociation constants (K(D)) for 37 neuroleptics and one metabolite of a neuroleptic (haloperidol metabolite) for the human serotonin, norepinephrine, and dopamine transporters with [3H]imipramine, [3H]nisoxetine, and [3H]WIN35428, respectively. Among neuroleptics, the four most potent compounds at the human serotonin transporter were triflupromazine, fluperlapine, chlorpromazine, and ziprasidone (K(D) 24-39 nM); and at the norepinephrine transporter, chlorpromazine, zotepine, chlorprothixene, and promazine (K(D) 19-25 nM). At the human dopamine transporter, only pimozide (K(D) = 69+/-3) ziprasidone (K(D) = 76+/-5) had notable potency. These data may be useful in predicting therapeutic and adverse effects, including drug interactions of neuroleptics.
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serotonin triflupromazine fluperlapine chlorpromazine ziprasidone norepinephrine chlorpromazine zotepine chlorprothixene promazine neuroleptics dopamine pimozide ziprasidone neuroleptics neuroleptics monoamine human serotonin, norepinephrine, and dopamine transporters human serotonin transporter norepinephrine transporter human dopamine transporter haloperidol human monoamine transporters serotonin norepinephrine dopamine [3H]imipramine [3H]nisoxetine [3H]WIN35428 neuroleptics