title: Phenytoin differentially modulates the affinity of agonist and antagonist ligands for sigma 1 receptors of guinea pig brain.
abstract: We evaluated the effects of phenytoin (DPH) on the affinity for sigma-1 (sigma(1)) receptors of agonist or antagonist sigma(1) ligands in guinea pig brain. Heterologous competition experiments showed that DPH (250 microM and 1 mM) concentration-dependently increased the affinity of the sigma(1) agonists dextromethorphan, (+)-SKF-10,047, (+)-3-PPP, and PRE-084. However, neither DPH 250 microM nor 1 mM increased (in fact, they slightly decreased) the affinity of the sigma(1) receptor antagonists haloperidol, BD 1063, NE-100, progesterone, and BD 1047. These findings suggest that allosteric modulation by DPH of the affinity of sigma(1) receptor ligands depends on the agonist or antagonist characteristics of the ligand. Therefore, determining in vitro the differential modulation by DPH of sigma(1) ligand affinity appears to constitute a procedure that can predict the pharmacological profile of different sigma(1) ligands.
authors.affiliation: Department of Pharmacology and Institute of Neuroscience, School of Medicine, University of Granada, 18012 Granada, Spain.
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Cobos
authors.forename: José M
authors.initials: JM
authors.lastname: Baeyens
authors.forename: Esperanza
authors.initials: E
authors.lastname: Del Pozo
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003915:Dextromethorphan / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D005029:Ethylenediamines / Q000494:pharmacology; D006168:Guinea Pigs; D006220:Haloperidol / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D017480:Receptors, sigma / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: C093337:1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine; D000840:Anisoles; D000927:Anticonvulsants; D005029:Ethylenediamines; D008024:Ligands; D009025:Morpholines; D010879:Piperazines; D010880:Piperidines; D011437:Propylamines; D017480:Receptors, sigma; C071738:2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C097963:N-(2-(3,4-Dichlorphenyl)ethyl)-N,N',N'-trimethyl-1,2-ethandiamin; D011374:Progesterone; D010672:Phenytoin; D003915:Dextromethorphan; C012134:SK&F 10047; C026539:preclamol; D010620:Phenazocine; D006220:Haloperidol