Trihexyphenidyl enhances physostigmine prophylaxis against soman poisoning in guinea pigs.
The protective effects of simultaneous and continuous administration of physostigmine and trihexyphenidyl against soman-induced toxicity were studied in guinea pigs. Not only did trihexyphenidyl reduce physostigmine-induced toxicity when it was administered continuously to the animals along with physostigmine, the combination afforded greater protection from soman lethality than did either agent administered alone. The combination pretreatment also gave better protection against soman-induced body weight loss and decreased water consumption and attenuated the down-regulation of cholinergic receptors which occurred when physostigmine alone was used. The onsets of other soman-induced toxicity signs were delayed significantly by the combination pretreatment regimen. These results suggest that simultaneous administration of the combination of physostigmine and trihexyphenidyl may be more useful than physostigmine alone as prophylaxis against soman poisoning.
Lim
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DK
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
Hoskins
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D004347:Drug Interactions; D006168:Guinea Pigs; D007700:Kinetics; D007928:Lethal Dose 50; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D010830:Physostigmine / Q000494:pharmacology*; D010890:Pirenzepine / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D012999:Soman / Q000037:antagonists & inhibitors* / Q000506:poisoning; D014282:Trihexyphenidyl / Q000494:pharmacology*
D008565:Membrane Proteins; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D014282:Trihexyphenidyl; D012999:Soman; D010830:Physostigmine