Cholinergic actions of diazepam and atropine sulfate in soman poisoning.
The effectiveness of diazepam alone or in the presence of atropine sulfate in reversing soman-induced convulsions, inhibition of blood and brain cholinesterase (ChE) activity, and elevation of brain acetylcholine (ACh) and choline (Ch) concentrations in rats was studied. Diazepam (5 mg/kg, IM) blocked the convulsive activity of soman (100 micrograms/kg, SC) whereas atropine sulfate (12 mg/kg, IM) did not. Inclusion of atropine sulfate enhanced the anticonvulsant effects of diazepam. Neither diazepam nor atropine sulfate alone affected ChE activity in the blood and brain of rats, nor did they alone, or in combination, reverse the ChE inhibition induced by soman. Diazepam by itself caused an increase in ACh concentrations in the striatum and a decrease in Ch concentrations in the cortex and striatum. On the other hand, atropine sulfate produced a decrease in ACh and an increase in Ch concentrations in these two brain regions. With combined treatment, diazepam reversed the effect of atropine sulfate on brain ACh and Ch concentrations. Diazepam attenuated the soman-induced elevation of ACh and Ch concentrations in most of the brain regions studied, while atropine sulfate did not. Only when diazepam was given concurrently with atropine sulfate did the elevated brain ACh or Ch concentrations induced by soman return to normal. These results suggest that the anticonvulsant activity of diazepam in soman poisoning may be partially related to its action on presynaptic cholinergic mechanism.
Shih
T M
TM
Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002800:Cholinesterase Inhibitors; D002802:Cholinesterases / Q000097:blood; D003975:Diazepam / Q000494:pharmacology*; D004912:Erythrocytes / Q000201:enzymology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009928:Organ Specificity; D010277:Parasympathomimetics; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D012999:Soman / Q000506:poisoning*
D002800:Cholinesterase Inhibitors; D010277:Parasympathomimetics; D001285:Atropine; D012999:Soman; D002802:Cholinesterases; D000109:Acetylcholine; D003975:Diazepam