6-(5-hydroxy-2-pyridylmethylamino)-9-beta-ribofuranosylpurine and Brain-Ischemia

The effect of AMG-1 [6(5-hydroxy-2-methylpyridylamino)-9 ribofranosylpurine] on mouse brain energy metabolism in complete brain ischemia induced by decapitation and on neurological deficit and histopathological changes after occlusion of the middle cerebral artery (MCAO) in rats were studied. The results indicate that AMG-1 has an effect of improving the status of energy metabolism in complete brain ischemia in mice. Lactate concentration was greatly reduced and the ATP and phosphocreatine levels were significantly elevated. Treatment with AMG-1 or nimodipine was performed before and after MCAO. The score of neurological deficit was significantly decreased as compared with the vehicle treated group. The extent of ischemic neuronal injury was determined by histopathological examination. AMG-1 and nimodipine seemed to attenuate the MCAO-induced neuronal damage. In as much as AMG-1 can improve the status of brain energy metabolism, neurological deficit and neuronal damage after ischemic insult, AMG-1 may have a beneficial effect for the treatment of cerebral ischemic damage.

Topics: Adenosine; Agaricales; Animals; Brain; Brain Ischemia; Energy Metabolism; Male; Mice; Nimodipine; Rats; Rats, Inbred Strains

The chemical structure of AMG-1 was isolated during our search for an effective compound to overcome the untoward effects of complete ischemia. The duration of gasping was prolonged significantly and dose-dependently in mice by the administration of AMG-1, the efficacy being 1000 times that seen with adenosine. However, AMG-1 had no effect on ischemia-induced passive avoidance impairment and histopathological degradation in CAl neurons in the hippocampus. The relationship between adenosine and its analogue and cerebral ischemia is discussed.

Topics: Adenosine; Animals; Brain Ischemia; Cell Survival; Gerbillinae; Hippocampus; Male; Mice; Mice, Inbred ICR; Motor Activity; Neurons; Pentobarbital; Sleep