TY - JOUR
T1 - [3H]opipramol labels a novel binding site and a receptors in rat brain membranes
AU - Ferris, Christopher D.
AU - Hirsch, David J.
AU - Brooks, Brian P.
AU - Snowman, Adele M.
AU - Snyder, Solomon H.
PY - 1991/2
Y1 - 1991/2
N2 - Opipramol (OP), a clinically effective antidepressant with a tricyclic structure, is inactive as an inhibitor of biogenic amine uptake. [3H]Opipramol binds saturably to rat brain membranes (apparent KD = 4 nM, Bmax = 3 pmol/mg of protein). [3H]Opipramol binding can be differentiated into haloperidol-sensitive and -resistant components, with Ki values for haloperidol of 1 nM (Bmax = 1 pmol/mg of protein) and 350 nM (Bmax = 1.9 pmol/mg of protein), respectively. The drug specificity of the haloperidol-sensitive component is the same as that of a receptors labeled with (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine. The halopendol-resistant component does not correspond to any known neurotransmitter receptor or uptake recognition site. It displays high affinity for phenothiazines and related structures such as perphenazine, clopenthixol, and flupenthixol, whose potencies are comparable to that of opipramol. Because certain of these drugs are more potent at the haloperidol-resistant opipramol site than in exerting any other action, it is possible that this opipramol-selective site may mediate their therapeutic effects.
AB - Opipramol (OP), a clinically effective antidepressant with a tricyclic structure, is inactive as an inhibitor of biogenic amine uptake. [3H]Opipramol binds saturably to rat brain membranes (apparent KD = 4 nM, Bmax = 3 pmol/mg of protein). [3H]Opipramol binding can be differentiated into haloperidol-sensitive and -resistant components, with Ki values for haloperidol of 1 nM (Bmax = 1 pmol/mg of protein) and 350 nM (Bmax = 1.9 pmol/mg of protein), respectively. The drug specificity of the haloperidol-sensitive component is the same as that of a receptors labeled with (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine. The halopendol-resistant component does not correspond to any known neurotransmitter receptor or uptake recognition site. It displays high affinity for phenothiazines and related structures such as perphenazine, clopenthixol, and flupenthixol, whose potencies are comparable to that of opipramol. Because certain of these drugs are more potent at the haloperidol-resistant opipramol site than in exerting any other action, it is possible that this opipramol-selective site may mediate their therapeutic effects.
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M3 - Article
C2 - 1847494
AN - SCOPUS:0025924671
SN - 0026-895X
VL - 39
SP - 199
EP - 204
JO - Molecular Pharmacology
JF - Molecular Pharmacology
IS - 2
ER -