Atropinized Heat-Stressed Rat Model: Anticholinergic and Anticholinesterase Drug Potency.

摘要

We have developed an animal model to evaluate the thermoregulatory effects of several anticholinergic drugs, particularly in hot environments. Our previous work on this model demonstrated that atropine, the prototype of muscarinic anticholinergic drugs, produces a dose-dependent increase in heating rate of heat-stressed rats that lasted for 3 hours after administration. By comparing the effects on heating rate of other anticholinergic drugs relative to the effects of atropine, we derived the following potency ratios: imipramine (0.004), amitriptyline (0.02), chlorpromazine (0.1), atropine (1), L-hyoscymaine (2), atropine methyl nitrate (4), and scopolamine (16). Additionally, we tested the ability of carbamates to reduce the elevated heating rate of atropinized rats as a measure of anticholinesterase efficacy, resulting in the following relative potencies: neostigmine (8), physostigmine (2) and pyridostigmine (1). Our results indicate that this is a useful model to evaluate potential drug-exacerbated increases in body temperature in hot environments.