title: New recreational drug 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (alpha-PVP) activates central nervous system via dopaminergic neuron.
abstract: 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP) is a new designer drug of the cathinone type. People who have taken drugs containing α-PVP or other synthetic cathinone reportedly lose consciousness, develop difficulty breathing, and at worst case, die. However, the mechanism underlying α-PVP-induced neurotoxicity is unknown. The objective of the present study was to investigate the effect of α-PVP on the central nervous system (CNS) and compare its neurotoxicity with that of methamphetamine (METH) in mice. Balb/c male mice (8 weeks old) were orally administered α-PVP (25 mg/kg) or METH (5 mg/kg). α-PVP induced a significant increase in locomotor activity, which occurred earlier than locomotor activity induced by METH. This increase was inhibited by the D1 receptor antagonist SCH23990 (50 µg/kg, i.p.) and the D2 receptor antagonist sulpiride (50 mg/kg, i.m.). The extracellular concentration of dopamine (DA) in the striatum, determined by in vivo microdialysis increased immediately after α-PVP administration. These results suggest that α-PVP stimulates DA release, causing an increase in locomotor activity, and that this stimulatory effect of α-PVP on CNS is mediated, at least in part, by the D1 and D2 receptors.
authors.affiliation: Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy.
authors.forename: Asuka
authors.initials: A
authors.lastname: Kaizaki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Numazawa
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D000697:Central Nervous System Stimulants; D003342:Corpus Striatum / Q000378:metabolism; D015198:Designer Drugs / Q000633:toxicity*; D004298:Dopamine / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D059290:Dopaminergic Neurons / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000633:toxicity; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010422:Pentanones / Q000494:pharmacology / Q000633:toxicity*; D011759:Pyrrolidines / Q000494:pharmacology / Q000633:toxicity*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D000697:Central Nervous System Stimulants; D015198:Designer Drugs; D065127:Dopamine D2 Receptor Antagonists; D010422:Pentanones; D011759:Pyrrolidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D008694:Methamphetamine; C000592273:1-phenyl-2-(1-pyrrolidinyl)-1-pentanone; D013469:Sulpiride; D004298:Dopamine