title: Effects of the novel thyrotropin-releasing hormone analogue Na -((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L-prol ina mide monohydrate on the central nervous system in mice and rats.
abstract: The central nervous system (CNS) effects of a novel thyrotropin-releasing hormone (TRH) analogue, JTP-2942 (Na-alpha- ((1S,2R)-2-methyl-4-oxocyclopentylcarbonyl)-L-histidyl-L-pro linamide monohydrate, CAS 131404-34-7) were investigated and compared with those of TRH. When administrated subcutaneously, JTP-2942 was about 80 times more potent than TRH in the antagonization of reserpine-induced hypothermia, and when administrated intravenously it was about 16 times more potent than TRH in the potentiation of flexor reflexes. Furthermore, oral administration of JTP-2942 was able to antagonize a chlorpromazine-induced reduction in locomotor activity, while TRH was far less effective. In tests on the recovery from pentobarbital-induced sleep and disturbance of consciousness induced by concussive head trauma, JTP-2942 was about 30 and 3 times more potent than TRH, respectively. Thus, JTP-2942 had a far stronger and more persistent action compared with TRH in regard to these effects. However, JTP-2942 had a 3-fold lower effect on thyroid stimulating hormone (TSH) release than TRH. These results suggest that the stimulatory effects of JTP-2942 are selective for the CNS and that this TRH analogue may be applicable to clinical use.
authors.affiliation: Department of Pharmacology, Japan Tobacco Inc., Kanagawa.
authors.forename: M
authors.initials: M
authors.lastname: Matsushita
authors.forename: F
authors.initials: F
authors.lastname: Yonemori
authors.forename: N
authors.initials: N
authors.lastname: Furukawa
authors.forename: A
authors.initials: A
authors.lastname: Ohta
authors.forename: K
authors.initials: K
authors.lastname: Toide
authors.forename: I
authors.initials: I
authors.lastname: Uchida
authors.forename: K
authors.initials: K
authors.lastname: Iwata
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001924:Brain Concussion / Q000523:psychology; D002490:Central Nervous System / Q000187:drug effects*; D002746:Chlorpromazine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003243:Consciousness / Q000187:drug effects; D003655:Decerebrate State / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D012110:Reserpine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects; D013972:Thyrotropin / Q000097:blood; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C080784:JTP 2942; D013973:Thyrotropin-Releasing Hormone; D012110:Reserpine; D013972:Thyrotropin; D010424:Pentobarbital; D002746:Chlorpromazine