Cleland's reagents block lethal and hypnotic effects of pentobarbital

We studied the effect of the reducing agents dithiothreitol and dithioerythritol (Cleland's reagents) on the hypnotic and toxic effects of pentobarbital in rodents. In pentobarbital anesthetized rats (50 mg/kg), the i.v. infusion of dithioerythritol (84 mumol/kg/min for 10 min) accelerated the return of eyeblink and righting reflexes (to 4 +/- 1 min vs. 22 +/- 2 min,k and 15 +/- 1 vs. 65 +/- 8 min respectively (P < 0.001). In mice receiving lethal doses of pentobarbital, the 4 h LD50 was 128 +/- 2 mg/kg; when dithioerythritol was given simultaneously, LD50 was > 165 mg/kg. Dithiothreitol also had a protective effect in rats. Oxidized dithiothreitol or dithioerythritol had no effect on pentobarbital sleeping time or mortality. The protective effect of dithioerythritol was dose-dependent; a high dose (294 mg/kg) gave complete protection in the short term, but killed the mice subsequently. The study shows that Cleland's reagents or their derivatives can act as pentobarbital antagonists in rodents, although side effects limit that usefulness. It also suggests caution in the use of dithiothreitol and related compounds during pentobarbital anesthesia.