Effects of NPC16377, a potent and selective sigma receptor ligand, on the activity of mesencephalic dopamine-containing neurons in the rat.
NPC16377 is a highly selective sigma receptor ligand with low affinity for other neurotransmitter receptors. Preclinical studies indicate that the drug exhibits a pharmacological profile similar to that previously ascribed to atypical antipsychotic drugs. In the present series of experiments, extracellular recording techniques were used to assess the acute effects of NPC16377 on the electrophysiological properties of mesencephalic dopamine-containing neurons in the rat. Systemic administration of NPC16377 produced marginal increases in the firing rate of these neurons but failed to fully reverse the inhibitory effects of the dopamine agonists apomorphine and d-amphetamine. Low doses of the drug potentiated the rate-decreasing effects of d-amphetamine in the substantia nigra but not in the ventral tegmental area. Some of these effects are similar to the actions of atypical antipsychotic drugs, while others appear to be unique to this compound and may involve a direct interaction with sigma sites.
Shepard
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Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228.
Lehmann
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Connelly
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects*
D014150:Antipsychotic Agents; D005419:Flavonoids; D010880:Piperidines; D017480:Receptors, sigma; C081310:6-(6-(4-hydroxypiperidinyl)hexyloxy)-3-methylflavone hydrochloride; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine