Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018991 (hemiplegia)
 3,997 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of YM-14673, a new thyrotropin-releasing hormone (TRH) derivative (N alpha-[[(S)-4-oxo-2-azetidinyl]carbonyl]- L-histidyl-L-prolinamide dihydrate), on the pyramidal motor system were studied in comparison with those of TRH in rats subjected to electrical destruction of the left internal capsule, a brain region of the pyramidal motor tract. In this model, neurological deficits such as hemiplegia and decrease of amplitude of electromyographic activity evoked by electrical stimulation of the left sensory motor cortex, were observed on the right legs. Drug administrations were started from 1 day after the surgical operation on and conducted once or several times a day for 13 days. YM-14673 (0.1 mg/kg, i.p., i.v., i.m.; 1 mg/kg, p.o.), unlike its metabolite (M-1) (10 mg/kg, i.p.), accelerated the recovery from neurological deficits. Decrease of evoked EMG activity on the 6th day after surgery was improved by administration of YM-14673 (0.1 mg/kg, i.p.). Intraperitoneal administration of TRH (1-10 mg/kg) once a day did not show any influence on neurological deficits. However, multiple i.p. administrations of TRH seven times in 1 hr accelerated recovery from deficits. These TRH activities are supported by metabolic studies which indicated that a high plasma level of TRH was maintained by multiple administrations of TRH. These results suggest that YM-14673 has a facilitatory effect on the pyramidal motor system which is due, in part, to its TRH-like properties.
 ...
PMID:Effects of YM-14673, a new TRH analogue, on behavioral and electrophysiological changes in rats subjected to electrical lesion of the internal capsule. 212 25

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.
 ...
PMID:Effects of a new thyrotropin-releasing hormone derivative on behavioral changes after focal cerebral ischemia in rats. 249 90

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.
 ...
PMID:Effects of YM-14673, a new TRH analogue, on neurological deficits in rats with experimental cerebral hematoma. 250

We investigated the effects of RGH-2202 (posatirelin, (-)-(2S)-N-[(1S)-1-[[(2S)-2-carbamoyl-1-pyrrolidinyl[carbonyl]-3- methylbutyl]-6-oxopipecolamide), a thyrotropin-releasing hormone (TRH) analog, on behavioral changes during a chronic phase of focal ischemia in rats in comparison with the parent peptide. The left middle cerebral artery (MCA) was occluded under halothane anesthesia, and the subsequent behavioral changes were observed for 35 days. RGH-2202 (1, 3, and 10 mg/kg) and TRH (10 mg/kg) were given IP just after the operation and afterward once a day for 14 days. MCA-occluded rats exhibited neurologic symptoms including hemiplegia and abnormal posture and disturbance of passive avoidance learning during the entire 35-day observation period. The repeated treatment with either peptides improved the neurologic and cognitive deficits. In addition, a recovery from deficits was still advanced after discontinuation of the drug treatment. In these effects, RGH-2202 was about three times more potent than TRH. Neural tissue damage in drug-treated groups, measured by omega 3 binding site densities 35 days after MCA occlusion, was included to be less than that in the vehicle-treated group. These results suggest that appropriate treatment with RGH-2202 may be useful in the treatment of functional disturbances after focal cerebral ischemia.
 ...
PMID:Effects of RGH-2202 on behavioral deficits after focal cerebral ischemia in rats. 858 7