Effects of YM-14673, a new TRH analogue, on neurological deficits in rats with experimental cerebral hematoma.
Effects of YM-14673, a new thyrotropin-releasing hormone (TRH) analogue, on neurological deficits were observed in comparison with those of TRH and citidine diphosphate choline (CDP-choline) in rats with an experimental hematoma. Unilateral cerebral hematoma was prepared by injection of 0.25 ml of autologous blood into the region around capsula interna, putamen and caudate nucleus of the left cerebral hemisphere of the rats. The drug was administered once or multiple times a day immediately after the surgical operation for 7 days and measurement of neurological deficits was conducted every day for 7 days. Neurological deficits, such as hemiplegia, were observed maximally on the 3rd day after the operation and then gradually recovered in the saline-treated group. YM-14673 (0.1, 0.3 mg/kg i.p.) accelerated the recovery of neurological deficits. Single i.p. administration of TRH did not affect the neurological deficits; however, multiple administration (7 times a day for 7 days) of TRH accelerated the recovery of neurological deficits. CDP-choline, a cerebral metabolic enhancer, even in a dose of 300 mg/kg (i.p.) did not show any influence on neurological deficits. These results suggest that YM-14673 ameliorated neurological deficits in the cerebral hematoma models, presumably due to TRH-like activity. Possible mechanisms of the pharmacological actions of YM-14673 are also discussed.
Yamamoto
M
M
Department of Pharmacology, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Shimizu
M
M
Kawabata
S
S
Terai
M
M
D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D001385:Azetines / Q000494:pharmacology*; D002543:Cerebral Hemorrhage / Q000503:physiopathology*; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D006406:Hematoma / Q000503:physiopathology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013973:Thyrotropin-Releasing Hormone / Q000097:blood / Q000494:pharmacology; D013997:Time Factors
D001384:Azetidines; D001385:Azetines; D004151:Dipeptides; D003566:Cytidine Diphosphate Choline; D013973:Thyrotropin-Releasing Hormone; C054995:azetirelin