Studying long-term effect of phenytoin either alone or combined with ascorbic acid on the anesthetic effect of urethane in rats

Phenytoin is an anticonvulsant drug known to interact with many other drugs. Previous data suggest that chronic administration of phenytoin delays urethane-induced loss of righting reflex (LRR) and this phenomenon being potentiated by concomitant administration of ascorbic acid (ASC). Therefore, we examined how phenytoin at two different doses combined or not with ASC (fixed dose) interact with both the latency to, and the duration for urethane-induced LRR in experimental rats. The results showed that lower dose of phenytoin (60 mg/kg rat b.i.d.) has significantly shortened the duration of LRR while higher dose of the drug (120 mg/kg b.i.d.) has delayed the latency to LRR (cut-off period of 15 min). Furthermore, addition of ASC to any of the two doses of phenytoin gave results similar to that observed for latency to and duration of LRR when phenytoin was given alone at the higher dose (120 mg/kg b.i.d.). Our data suggest a resistant effect of chronic administration of phenytoin on latency to and/or duration of loss righting reflex induced by urethane in experimental animals. A dose-response relationship of phenytoin in this regard is expected and needs further investigations. The resistant effect of phenytoin on righting reflex has been augmented when ASC was chronically given in combination. This result supports a possible interaction between the two drugs and needs further investigations at both experimental and clinical levels.