Neuroprotective Effects of the Pyrrolopyrimidine U-104067F in 3-Acetylpyridine-Treated Rats

Abstract

The neuroprotective effects of U-104067F [(9-(2-morpholinyl)ethyl)2,4-di-l-pyrrolidinyl-9H-pyrimidino(4,5-b)indole monohydrochloride hydrate], a pyrrolopyrimidine antioxidant, were investigated in 3-acetylpyridine (3-AP)-treated Wistar rats. A significant (P<0.01) reduction in cerebellar cGMP and ATP was observed at 96 h after treatment with 3-AP (500 μmol/kg ip). Oral administration of U-104067F significantly attenuated 3-AP-induced reductions in cGMP and ATP, and this effect was dose related. Consistent with the neurochemical effect, U-104067F prevented 3-AP-induced loss of motor coordination. 3-Acetylpyridine produced a significant (P<0.01) loss of neurons in the inferior olivary nucleus. Treatment with U-104067F partially, but significantly (P<0.01), prevented the loss of inferior olivary neurons. The physiological and neurochemical parameters were maintained within normal limits by U-104067F in 3-AP-treated rats despite only partial preservation of inferior olivary neurons.