Anticholinergics: effects on thermoregulation and performance in rats.
Atropine (AT) induces a dose-dependent increase in rate of rise of core temperature (heating rate) in sedentary heat-stressed rats, a muscarinic anticholinergic (MA) effect which is quantitatively similar to the increase in heating rate seen in heat-exposed men after equivalent atropine dose. In the heat-stressed rat, scopolamine (S) was found to have 16 x the MA effect of AT and, in the present study, aprophen (AP) and trihexyphenidyl (THP) manifested 0.067 x 0.061 x the MA effect of AT. In rats exercising on a treadmill (11 m/min, 6 degrees incline, 26 degrees C), physostigmine (PH) administration resulted in reduced endurance and increased heating rate, both of which were attenuated following AT administration-hypothesized to be a nicotinic anticholinergic (NA) effect. Optimum doses of anticholinergics to reverse the PH-induced decrements were: AT-200 micrograms/kg, S-8-16 micrograms/kg, AP-3000 micrograms/kg, and THP-800 micrograms/kg. These optimum NA doses for AT, S, and AP were the same as those predicted from their MA potency relative to AT in heat-stressed rats. However, it should be noted that 800 micrograms/kg of THP is only 1/4 of the expected 3200 micrograms/kg dose of THP based on MA equivalence to AT. Relative MA activities and optimum doses in PH-treated exercising rats appear to be due to differential MA and NA activities. Thus, a combination of both sedentary heat-stressed and exercising rat models may be useful in predicting relative cholinergic effects of new drugs with both MA and NA effects in man.
Matthew
C B
CB
U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760-5007.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001286:Atropine Derivatives / Q000494:pharmacology; D001833:Body Temperature Regulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology*; D005082:Physical Exertion; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects
D001286:Atropine Derivatives; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D001285:Atropine