Potentiating effects of chlorpromazine on the paralysis and toxicity induced by guaiacal glyceryl ether in rats

Abstract

The effect of chlorpromazine (CPZ) on guaiacol glyceryl ether (GGE) induced paralysis and toxicity was studied in rats. Pretreatment with CPZ potentiated the duration of paralysis and increased the toxicity of GGE. The magnitude of potentiation of the paralysis was directly related to the dose of CPZ. The mechanism of potentiation was not linked with the inhibitory effect of CPZ on the hepatic microsomal enzymes responsible for inactivation of GGE, since the plamsa concentration of GGE in both saline and CPZ pretreated rats was the same at all time intervals after GGE administration. The LD100 dose of GGE in rats pretreated with 10 mg/kg CPZ was 1000 mg/kg. This dose killed only 50% of rats pretreated with saline. An age-dependent susceptibility to the paralytic effect of GGE as well as to the potentiating effect of CPZ was also noticed. The duration of paralysis caused by GGE at 750 mg/kg was 80% longer in the younger (35–45 days old) than in the older (125–135 days old) rats. The potentiating effect of GGE by CPZ was, however, much more pronounced in the latter. In view of the extensive concomitant uses of GGE and CPZ in therapy, it was suggested that the indiscriminate use of their dosages in combination might lead to an unfavorable interaction.