Effects of cadmium and verapamil on ketamine-induced anesthesia in mice

Previous studies have shown that pretreatment with cadmium and verapamil potentiated the effects of some CNS active drugs. The objective of this study was to determine the influence of these agents on ketamine anesthesia in adult male mice. Intraperitoneal administration of 300 mg ketamine/kg produced sleeping time of 40.88 +/- 2.98 min. Pretreatment with a single dose of either 3 mg cadmium/kg sc or 5 mg verapamil/kg ip alone significantly increased the duration of sleeping time (40.88 +/- 2.98 vs 55.09 +/- 4.20 and 49.01 +/- 3.09 min). Pretreatment with cadmium plus verapamil produced significant additive effects on ketamine-induced anesthesia (40.88 +/- 2.98 vs 70.32 +/- 4.64 min). Pretreatment with 3 mg cadmium/kg sc before 1 w caused a reduction in the potentiating effects of a 2nd dose of cadmium in ketamine-induced anesthesia in mice. These results indicate that prolongation of ketamine-induced anesthesia by cadmium and verapamil could be mediated either by inhibition of hepatic P450 metabolizing enzymes or neuronal calcium channels blockade. The tolerance to the potentiating effects of cadmium could be mediated by hepatic metallothionein induction and a reduction in total body cadmium burden.