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662097 
Journal Article 
Abstract 
Comparison of Diphenhydramine, Glycopyrrolate, and Atropine in the Treatment of Organophosphate Poisoned-Mice 
Schaeffer, TH; Hung, OL; Shih, RD 
2004 
1 
Journal of Toxicology: Clinical Toxicology
ISSN: 0731-3810
EISSN: 1097-9875 
TOX/5002625 
42 
5 
797-798 
English 
Objective: Treatment of acute organophosphate poisoning includes the use of the antidote atropine. However, mass casualties from organophosphate poisoning may quickly outstrip the supply of available atropine. Few studies have evaluated other anticholinergic agents as potential antidotes. We attempted to compare the effectiveness of the anticholinergics: diphenhydramine, glycopyrrolate, and atropine in treating organophosphate poisoned mice. Methods: A dose-lethality curve was calculated for the organophosphate dichlorvos. Maximal safe doses of all antidotes were determined. All mice received IP pretreatment with the antidote (glycopyrrolate, diphenhydramine, or atropine) or an equivalent volume NS control followed in 5 min by IP injection of dichlorvos. Mice were observed for the onset of seizure activity and time to death up to 24 h. Results: The maximal safe dose of IP diphenhydramine, glycopyrrolate, and atropine was 50 mg/kg, 120 mg/kg, and 180 mg/kg, respectively. Diphenhydramine, glycopyrrolate, and atropine did not affect the onset of seizure activity or time to death in comparison to controls. In dichlorvos poisoned mice (35 mg/kg), the mortality rate for the pretreatment antidotes were diphenhydramine (50 mg/kg), 100% (p=NS); glycopyrrolate (90 mg/kg), 40% (p=0.02); and atropine (50 mg/kg), 0% (p=0.01). The mortality rate for the control group at this dose was 100%. At a lower dose of dichlorvos (30 mg/kg), the mortality rate of diphenhydramine pretreated mice (50 mg/kg) was 40% vs. 100% for controls, (p=0.04). Conclusion: Both diphenhydramine and glycopyrrolate pretreatment decreased mortality in dichlorvos-poisoned mice. However, neither drug was as effective as atropine. 
Mice; Animals; Comparative Study; Phosphoric Acid Esters/*POISONING; Poisoning/ETIOLOGY/DRUG THERAPY; Diphenhydramine/*THERAPEUTIC USE/ADMINISTRATION & DOSAGE; Glycopyrrolate/*THERAPEUTIC USE/ADMINISTRATION & DOSAGE; Atropine/*THERAPEUTIC USE/ADMINISTRATION & DOSAGE; Cholinergic Antagonists/*THERAPEUTIC USE/ADMINISTRATION & DOSAGE; Dichlorvos/POISONING; Dose-Response Relationship, Drug; NO CAS RN; 58-73-1; 596-51-0; 51-55-8; 62-73-7