Physostigmine: dose-response effects on endurance and thermoregulation during exercise.
We previously reported that the administration of 200 micrograms/kg of physostigmine (PH) to rats exercising on a treadmill resulted in decrements in both endurance (decreased running time to exhaustion) and thermoregulation. However, it was necessary to determine the dose-response effects of PH administration before PH-treated exercising rats could be used as a model with which to examine the relative anticholinergic potency of drugs. In the present work saline, 50, 100, or 200 micrograms/kg of physostigmine salicylate (0%, 40%, 50%, and 60% whole blood cholinesterase inhibition) was administered to rats (N = 12/group) prior to treadmill exercise (26 degrees C, 50% rh, 11 m/min, 6 degrees incline). The saline control group ran for 67 +/- 6 min (mean +/- SE) with a rate of rise of core temperature of 0.051 +/- 0.007 degrees C/min. The run times declined (80%, 64% and 48% of control) as rate of rise of core temperature increased (116%, 180%, and 214% of control) in a dose-dependent manner (50, 100, 200 micrograms/kg PH). Cholinergic symptoms such as salivation, tremors, and defecation were also affected in a dose-dependent manner by PH administration. Since cholinergic symptoms, thermoregulatory effects, and endurance decrements all vary in a dose-dependent manner with physostigmine administration, the exercising rat represents a useful model for examining the relative potency of cholinergic therapies.
Matthew
C B
CB
US Army Res. Inst. of Environmental Med., Natick, MA 01760-5007.
Francesconi
R P
RP
Hubbard
R W
RW
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010807:Physical Endurance / Q000187:drug effects*; D005082:Physical Exertion / Q000502:physiology*; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010830:Physostigmine