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Anticholinergics: effects on thermoregulation and performance in rats
1U.S. Army Research Institute of Environmental Medicine, Natick, MA 01760-5007.
Neuroscience and Biobehavioral Reviews
|January 1, 1991
Summary
This study shows that combining sedentary and exercising rat models can predict the cholinergic effects of new drugs in humans. Different anticholinergic drugs exhibit varying muscarinic and nicotinic activities.
Area of Science:
- Pharmacology
- Physiology
- Drug Discovery
Background:
- Atropine (AT) increases core body temperature in heat-stressed rats, similar to effects observed in humans.
- Anticholinergic drugs can have both muscarinic (MA) and nicotinic (NA) effects, influencing thermoregulation and exercise performance.
- Physostigmine (PH) impairs exercise endurance and increases heating rate, suggesting a role for cholinergic systems in exercise physiology.
Purpose of the Study:
- To compare the muscarinic and nicotinic anticholinergic activities of various drugs using sedentary and exercising rat models.
- To determine if these models can predict the cholinergic effects of new drugs in humans.
- To investigate the differential effects of scopolamine (S), aprophen (AP), and trihexyphenidyl (THP) on thermoregulation and exercise.
Main Methods:
- Sedentary heat-stressed rats were used to assess muscarinic anticholinergic (MA) effects.
- Exercising rats (treadmill) were used to evaluate nicotinic anticholinergic (NA) effects and drug interactions with physostigmine (PH).
- Dose-response relationships were established for atropine (AT), scopolamine (S), aprophen (AP), and trihexyphenidyl (THP).
Main Results:
- Scopolamine (S) exhibited 16 times the MA effect of atropine (AT) in heat-stressed rats.
- Aprophen (AP) and trihexyphenidyl (THP) showed significantly lower MA effects compared to atropine.
- In exercising rats, optimal doses of AT, S, and AP to reverse physostigmine-induced decrements correlated with their MA potencies, but trihexyphenidyl (THP) showed differential activity.
Conclusions:
- Differential muscarinic and nicotinic activities of anticholinergic drugs influence their effects on thermoregulation and exercise.
- Combining sedentary heat-stressed and exercising rat models provides a comprehensive approach to predict the cholinergic effects of novel drugs in humans.
- This dual-model system is valuable for understanding drug actions with both MA and NA properties.