Atropine sulfate and 2-pyridine aldoxime methylchloride elicit stress-induced convulsions and lethality in mice and guinea pigs.
The present study demonstrates that dose combinations of atropine sulfate and 2-pyridine aldoxime methylchloride (2-PAM), which do not produce any overt toxic effects on the behavior of mice or guinea pigs in a stable environment, elicit clonic-tonic convulsions and death when the animals are physically stressed by cold water swimming. Phenoxybenzamine (1-6 mg/kg), diazepam (0.625 and 1.25 mg/kg) and pilocarpine (2.5 and 5 mg/kg) significantly decreased (or abolished) the occurrence of atropine and 2-PAM stressed-induced convulsions and/or lethality. In contrast, propranolol (20 mg/kg), was ineffective in preventing either convulsions or lethality. Changes in plasma glucose levels and internal body temperature did not appear to explain the precipitation of convulsions or ensuing death. These results suggest that during acute physical stress, relatively low doses of atropine and 2-PAM produce toxic and lethal effects due to the activation of alpha-adrenergic mechanisms along with a concomitant inactivation of cholinergic mechanisms.
D000818:Animals; D001285:Atropine / Q000633:toxicity*; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D003080:Cold Temperature; D003975:Diazepam / Q000494:pharmacology; D004347:Drug Interactions; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011220:Pralidoxime Compounds / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced* / Q000517:prevention & control; D013045:Species Specificity; D013312:Stress, Physiological / Q000150:complications*; D013550:Swimming; D013997:Time Factors
D001786:Blood Glucose; D011220:Pralidoxime Compounds; D001285:Atropine; C028797:pralidoxime; D003975:Diazepam