Beneficial effects of ME3167 (rolipram) on behavioral deficits in rats suffering from cerebral ischemia

• Published in: Japanese Journal of Pharmacology Vol. 61; no. suppl.1; p. 183
• Main Authors: Imanishi, Taiichiro, Ichimaru, Yasuyuki, Sawa, Aiko
• Format: Journal Article
• Language: Japanese; English
• Published: The Japanese Pharmacological Society 1993
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)51608-0

Effect of 4-「3-(cyclopentyloxy)-4-methoxyphenyl」-2-pyrrolidinone (rolipram), which is a selective inhibitor of cyclic AMP-specific phosphodiesterase (PDE-IV), on behavioral deficits induced by cerebral ischemia was examined in rats. Transient ischemia introduced by four-vessel occlusion for twenty minutes elicited disturbance of consciousness which was observed as disappearance of righting reflex and spontaneous movement immediately after reperfusion, decrease in body weight, impairment of passive avoidance response and delayed neuronal death in hippocampal CA1 region 7 days after ischemia. Administration of rolipram at 0.1 and 1 mg/kg, ip twice a day from twenty minutes before to 7 days after ischemia shortened the duration of disturbance of consciousness and reversed decrease in body weight at 0.1 and 1 mg/kg. It also improved the passive avoidance impairment and provided slight protection from the neuronal death at 0.1 and 1 mg/kg, respectively. In another experiment, single administration of rolipram prolonged survival periods in permanent ischemic rats at 1 mg/kg, ip. These results suggest the usefulness of rolipram in clinical treatment of cerebrovascular disorders.