Intoxication by benzodiazepines: studies with diazepam used as a model compound suggest an interaction with red blood cells calmodulin dependent (Ca2+, Mg2+) ATPase.
20 patients under therapy or intoxicated by benzodiazepines were studied. A partial inhibition of (Ca2+, Mg2+)ATPase on 'B' membranes (CaM rich membranes) was evident in 2 cases. A total inhibition of (Ca2+, Mg2+) ATPase on both 'B' and 'A' (CaM depleted) membranes was noted in 1 case: the patient who was severely intoxicated had pronounced hemolysis. As an attempt to elucidate the mechanism of this action, the effect of diazepam chosen as model compound was studied on 'B' and 'A' membranes prepared from normal human RBC previously incubated with diazepam. A high concentration of diazepam, corresponding to a 20-fold therapeutic level results in a 50% inhibition of the maximal activity of the enzyme on 'B' membranes. It may be speculated from these experiments that the effect of high concentration of benzodiazepines on CaM dependent (Ca2+, Mg2+) ATPase leads to accelerated RBC destruction.
D001569:Benzodiazepines / Q000506:poisoning; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002147:Calmodulin / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques
D002147:Calmodulin; D001569:Benzodiazepines; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D003975:Diazepam