Biochemical, behavioral, and electrophysiologic actions of the selective sigma receptor ligand (+)-pentazocine.
Research on the sigma receptor, a binding site associated with drug-induced psychotomimetic behaviors, has been hampered because most sigma agonists also interact with the phencyclidine (PCP) receptor. (+)-Pentazocine, a human psychotogen, is a selective sigma receptor ligand. To demonstrate sigma receptor activities, we studied the behavioral and electrophysiologic actions for (+)-pentazocine. In the behavioral drug discrimination procedure in which rats were trained to discriminate between 2.0 mg/kg (5.59 mumol/kg) (+)-pentazocine and saline, (+)-pentazocine produced dose-related increases in the percentage of trials completed on the (+)-pentazocine lever. At a dose of 1.0 mg/kg (3.29 mumol/kg) (+)-N-allylnormetazocine generalized completely to (+)-pentazocine. By contrast, PCP only partially generalized. In the visual evoked potential test, these compounds produced a significant dose-dependent slowing of the N2 latency. This response was prevented by haloperidol pretreatment. These results demonstrate pharmacologic actions for the selective sigma receptor ligand (+)-pentazocine and suggest some overlapping pharmacologic properties of the sigma and PCP receptor sites despite differences in central nervous system distribution.
Steinfels
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E.I. du Pont de Nemours & Co., Inc., Medical Products Department, Wilmington, Delaware 19898.
Alberici
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GP
Tam
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Cook
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D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D004193:Discrimination Learning / Q000187:drug effects*; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D008297:Male; D008566:Membranes / Q000378:metabolism; D010423:Pentazocine / Q000378:metabolism / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011957:Receptors, Opioid / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D012016:Reference Values
D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine; D010423:Pentazocine