Neuroprotective effects of the pyrrolopyrimidine U-104067F in 3-acetylpyridine-treated rats.
The neuroprotective effects of U-104067F[(9-(2-morpholinyl)ethyl) 2,4-di-l-pyrrolidinyl-9H-pyrimidino (4,5-b)(4,5indole 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 micromol/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.
Sethy
V H
VH
CNS Research, The Upjohn Company, Kalamazoo, Michigan 49001, USA.
Wu
H
H
Oostveen
J A
JA
Hall
E D
ED
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002452:Cell Count / Q000187:drug effects*; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018696:Neuroprotective Agents; D011725:Pyridines; D011743:Pyrimidines; D011759:Pyrrolidines; C010835:3-acetylpyridine; C096239:U 104067; D000255:Adenosine Triphosphate; D006152:Cyclic GMP