title: Pharmacological profile of neuroleptics at human monoamine transporters.
abstract: 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.
authors: Mayo Clinic Jacksonville, FL 32224, USA.
authors: M
authors: M
authors: Tatsumi
authors: K
authors: K
authors: Jansen
authors: R D
authors: RD
authors: Blakely
authors: E
authors: E
authors: Richelson
mesh_terms: D014150:Antipsychotic Agents / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002746:Chlorpromazine / Q000737:chemistry / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives / Q000378:metabolism; D003984:Dibenzazepines / Q000737:chemistry / Q000378:metabolism; D003988:Dibenzothiepins / Q000737:chemistry / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007099:Imipramine / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010868:Pimozide / Q000737:chemistry / Q000378:metabolism; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011869:Radioligand Assay; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism; D014273:Triflupromazine / Q000737:chemistry / Q000378:metabolism; D014316:Tritium
chemical_list: D014150:Antipsychotic Agents; D002352:Carrier Proteins; D003984:Dibenzazepines; D003988:Dibenzothiepins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D010879:Piperazines; D011993:Recombinant Fusion Proteins; C493227:SLC6A2 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D013844:Thiazoles; D005473:Fluoxetine; D014316:Tritium; C011386:nisoxetine; D010868:Pimozide; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; C092292:ziprasidone; C041528:fluperlapine; D003042:Cocaine; D007099:Imipramine; D014273:Triflupromazine; C022172:zotepine; D002746:Chlorpromazine