Protective effect of calmodulin inhibitors against acute cyanide-induced lethality and convulsions in mice.
The ED50 value of cyanide as measured by induction of convulsions (tonic seizure) was significantly increased by 80% or 69% when trifluoperazine (TFP) or chlorpromazine (CHP), a specific calmodulin inhibitor was preinjected intracerebroventricularly (i.v.t.) at a dose of 0.09 mumol/body of mice. However, the ED50 of cyanide was not significantly changed by the same dose of promethazine (PMZ), another calmodulin inhibitor. Since it is known that the inhibitory effect of TFP or CHP against calmodulin-dependent enzymes such as phosphodiesterase is 100-400-fold higher compared to PMZ, it is speculated that the inhibitory effect of TFP or CHP against cyanide-induced convulsions may be based on its strong inhibitory properties into calmodulin-dependent enzymes. On the other hand, the LD50 value of cyanide was significantly increased by i.v.t. preadministration of TFP or CHP (0.045 mumol/body). Furthermore, the LD50 value of cyanide was also significantly increased by the same dose of PMZ. These results suggest that there is no positive correlation between mortality and convulsions induced by cyanide.
Yamamoto
H
H
Department of Environmental Medicine, University of Tsukuba, Ibaraki, Japan.
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002746:Chlorpromazine / Q000627:therapeutic use; D003486:Cyanides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011398:Promethazine / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D014268:Trifluoperazine / Q000627:therapeutic use
D000927:Anticonvulsants; D002147:Calmodulin; D003486:Cyanides; D014268:Trifluoperazine; D011398:Promethazine; D002746:Chlorpromazine