title: Haloperidol treatment differentially regulates [3H]DTG and [3H](+)-3-PPP labeled sigma binding sites.
abstract: The effect of repeated haloperidol administration on sigma binding sites in brain membranes was assessed using [3H](+)-3-(3-hydroxyphenyl)-N-(1- propyl)piperidine ((+)-3-PPP) and [3H]1,3-di-o-tolylguanidine (DTG). Administration of haloperidol (1 mg/kg, i.p.) to guinea pigs for 14 consecutive days followed by a 4 day drug-free period prior to sacrifice resulted in 75% and 6% decreases in the specific binding of [3H](+)-3-(3-hydroxyphenyl)-N-(1- propyl)piperidine and [3H]1,3-di-o-tolylguanidine, respectively, when measured using a single concentration (2 nM) of radioligand. Scatchard analysis revealed a reduction in both the maximum number of [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine binding sites and the affinity of these sites for the radioligand; the potency of 1,3-di-o-tolylguanidine to inhibit [3H](+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine binding was also reduced. In parallel studies, the potency of 1,3-di-o-tolylguanidine to inhibit [3H]1,3-di-o-tolylguanidine binding was unaffected by haloperidol treatment, but the potency of (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine against [3H]1,3-di-o-tolylguanidine was reduced 3-fold. Phenytoin, which increased (10-fold) the potency of dextromethorphan to inhibit [3H]1,3-di-o-tolylguanidine binding in control membranes, had no effect in membranes obtained from haloperidol-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Scios-Nova, Inc., Baltimore, MD 21224-6522.
authors.forename: M A
authors.initials: MA
authors.lastname: Bailey
authors.forename: E W
authors.initials: EW
authors.lastname: Karbon
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism; D004334:Drug Administration Schedule; D006146:Guanidines / Q000378:metabolism*; D006168:Guinea Pigs; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010672:Phenytoin / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism*; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D015259:Dopamine Agents; D006146:Guanidines; D010880:Piperidines; D017480:Receptors, sigma; D010672:Phenytoin; C026539:preclamol; D006220:Haloperidol; C050232:1,3-ditolylguanidine