TY - JOUR
T1 - Pharmacological profile of neuroleptics at human monoamine transporters
AU - Tatsumi, Masahiko
AU - Jansen, Karen
AU - Blakely, Randy D.
AU - Richelson, Elliott
N1 - Funding Information:
This work is supported by Mayo Foundation for Medical Education and Research and USPHS grant MH27692 from N.I.M.H. We thank Drs. Zdenek B. Pristupa and H.B. Niznik, University of Toronto, Toronto, Canada, for supplying a cDNA encoding the human dopamine transporter. We also thank Terry Souder and Jennifer Stables for some technical assistance.
PY - 1999/3/5
Y1 - 1999/3/5
N2 - 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. Copyright (C) 1999 Elsevier Science B.V.
AB - 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. Copyright (C) 1999 Elsevier Science B.V.
KW - 5-HT (5-hydroxy-hyptamine, serotonin), human
KW - Dopamine transporter, human
KW - Neuroleptic
KW - Norepinephrine transporter, human
KW - Radioligand binding assay
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U2 - 10.1016/S0014-2999(99)00005-9
DO - 10.1016/S0014-2999(99)00005-9
M3 - Article
C2 - 10193665
AN - SCOPUS:0032979135
SN - 0014-2999
VL - 368
SP - 277
EP - 283
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -