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
vascular diseases.