A heat-stressed rat model to determine relative anticholinergic and anticholinesterase drug potency.
We have reported that atropine, the prototype of muscarinic anticholinergic drugs, elicits a dose-dependent increase in core temperature of heat-stressed rats. In the present study, we have quantified the effects of other anticholinergic drugs on increments in core temperature and have derived the following potencies relative to atropine: imipramine 0.004, amitriptyline 0.02, chlorpromazine 0.1, atropine 1, L-hyoscyamine 2, atropine methyl nitrate 4, and scopolamine 16. Additionally, we quantified the efficacy of carbamates to reduce the elevated heating rate of atropinized rats as a measure of anticholinesterase efficiency. The results indicated the following relative potencies: neostigmine 8, physostigmine 2, and pyridostigmine 1. We have concluded that alterations in core temperature responses to exposure to hot environments may be a useful and sensitive bioassay for anticholinergic and anticholinesterase efficacy.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002802:Cholinesterases / Q000097:blood; D006358:Hot Temperature; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012472:Salivation / Q000187:drug effects; D013312:Stress, Physiological / Q000503:physiopathology*; D014554:Urination / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D010276:Parasympatholytics; D001285:Atropine; D002802:Cholinesterases