Effects of a new thyrotropin-releasing hormone derivative on behavioral changes after focal cerebral ischemia in rats.
We observed the effects of a new thyrotropin-releasing hormone derivative, YM-14673 (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]-L-histidyl-L-prolinamide dihydrate), on behavioral changes in rats for 3 weeks after focal cerebral ischemia. Under halothane anesthesia, the left middle cerebral artery was occluded via a transretro-orbital approach. YM-14673 was administered just after the operation and once a day for 3 weeks. Neurologic deficits, including hemiplegia and abnormal posture, and disturbance of passive avoidance learning were present in solvent-treated control rats for the entire 3 weeks. YM-14673 at 0.1 or 0.3 mg/kg i.p. or 1 mg/kg p.o. significantly accelerated the recovery of neurologic deficits and ameliorated cognitive disturbance compared with the solvent-treated controls although the drug at 0.1 and 0.3 mg/kg i.p. did not influence the size of the ischemic infarct. YM-14673 mitigated the behavioral disturbances in this model of chronic focal cerebral ischemia. We also discuss the suitability of this model for the evaluation of drugs.
Yamamoto
M
M
Department of Pharmacology, Yamanouchi Pharmaceutical Co. Ltd., Tokyo, Japan.
Tamura
A
A
Kirino
T
T
Shimizu
M
M
Sano
K
K
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001384:Azetidines / Q000494:pharmacology*; D001385:Azetines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology / Q000523:psychology*; D002544:Cerebral Infarction / Q000473:pathology; D004151:Dipeptides / Q000494:pharmacology*; D008297:Male; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives*
D001384:Azetidines; D001385:Azetines; D004151:Dipeptides; D013973:Thyrotropin-Releasing Hormone; C054995:azetirelin