Pharmacological actions of a new TRH analogue, YM-14673, in rats subjected to cerebral ischemia and anoxia

European Journal of Pharmacology
M YamamotoH Okamiya

Abstract

The cerebral protective actions of a new thyrotropin releasing hormone (TRH) analogue, YM-14673, [Na-[[(S)-4-oxo-2-azetidinyl-carbonyl]-L-histidyl-L-prolinamide] dihydrate), were compared with those of CDP-choline (cerebral metabolic enhancer) and naloxone in rats rats subjected to unilateral carotid artery ligation and anoxic exposure (Levine rats). Drugs were administered intraperitoneally or orally 20, 80, and 140 min after anoxia. YM-14673 (0.03 to 1 mg/kg i.p. and 0.3 to 10 mg/kg p.o.) decreased the incidence of neurological deficits, such as hemiplegia and convulsion followed by coma and death, for 48 h after ischemia and anoxia. Both the increase in the brain water content and the degeneration of neurons in the cerebral cortex and thalamus were prevented by YM-14673 at a dose of 0.1 mg/kg (i.p.). CDP-choline (400 mg/kg i.p.), which is currently used in the therapy of cerebral vascular diseases, and naloxone (3 mg/kg i.p.) also decreased the incidence of the neurological deficits. These results suggest that YM-14673 protects Levine rats against neurological deficits, presumably by attenuating the development of brain edema and preventing neuronal damage. This compound may be useful in the therapeutic treatment of cerebral...Continue Reading

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Citations

Oct 13, 2001·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·K RejdakP Grieb
May 10, 2003·Neurobiology of Learning and Memory·N M W J De BruinL M Broersen
Apr 1, 1997·Journal of Pediatric Surgery·M D KleinA M Smith
Jan 2, 2004·The International Journal of Neuroscience·Süreyya Ataus AtausSevin Balkan
Oct 2, 1998·Stroke; a Journal of Cerebral Circulation·W ClarkK Hazel
Dec 3, 1999·Stroke; a Journal of Cerebral Circulation·W M ClarkR E Gammans

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