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.