title: Effect of JTP-2942, a novel thyrotropin-releasing hormone analogue, on pentobarbital-induced anesthesia in rats.
abstract: The effects of a novel thyrotropin-releasing hormone (TRH) analogue, N alpha-((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L-pro linamide monohydrate (JTP-2942), on pentobarbital-induced anesthesia in rats were investigated and compared with those of TRH. Intravenous administration of both JTP-2942 and TRH caused a dose-dependent decrease in the recovery time from pentobarbital-induced anesthesia. The minimum effective doses of JTP-2942 and TRH were respectively 0.03 and 1 mg/kg. The effect of JTP-2942 was antagonized by intraperitoneal scopolamine (0.5 mg/kg). Intraperitoneal JTP-2942 (1 mg/kg) caused an increase of acetylcholine release and a decrease of choline release in the frontal cortex and hippocampus of pentobarbital-treated rats. In addition, JTP-2942 ameliorated the decrease of hemicholinium-3-sensitive high-affinity choline uptake and the increase of acetylcholine in these brain regions. However, JTP-2942 had no effect on choline acetyltransferase activity or the choline content, which were also not changed by pentobarbital. Our results indicate that the effect of JTP-2942 on pentobarbital-induced anesthesia was about 30 times more potent than that of TRH, and suggest that JTP-2942 may act by accelerating acetylcholine turnover.
authors.affiliation: Central Pharmaceutical Research Institute, Japan Tobacco Inc., Osaka.
authors.forename: M
authors.initials: M
authors.lastname: Matsushita
authors.forename: F
authors.initials: F
authors.lastname: Yonemori
authors.forename: A
authors.initials: A
authors.lastname: Hamada
authors.forename: K
authors.initials: K
authors.lastname: Toide
authors.forename: K
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000109:Acetylcholine / Q000032:analysis; D000758:Anesthesia; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002794:Choline / Q000032:analysis / Q000378:metabolism; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C080784:JTP 2942; D013973:Thyrotropin-Releasing Hormone; D010424:Pentobarbital; D002794:Choline; D000109:Acetylcholine