Thermoregulatory, Endurance and Ultrastructural Effects of Acute and SubchronicPyridostigmine Bromide Administration in the Exercising Rat

摘要

Pyridostigmine (PY) is the drug currently approved for chemical agentprophylaxis. Previous studies have demonstrated that acute administration or high doses of PY have resulted in thermoregulatory, endurance and ultrastructural abnormalities. In this study the effects of acute (APY, 100 ug/kg, iv) and subchronic PY for 2, 3, and 4 weeks (PY2, PY3, PY4, 20 ug/hr, via osmotic pump) administration on treadmill endurance when measured in rats to determine whether any voluntary muscle weakness occurs as a result of PY administration. APY rats had reduced endurance time (56 + 18 min (mean + SD) vs 72 1 17) compared to saline controls and increased core temperatures at the start of exercise (Tc, 38.9 + o . 2oC vs 38.5 + 0. 6oC). These decrements were arneliorated with subchronic administration, and PY2 animals maintained lower Tc than SAL2 animals. Typical mitochondrial lesions detected with acute high doses of PY (lmg/kg) were not observed in any of these specimens. Decrements in endurance and thermoregulation and ultrastructural abnormalities previously seen with acute PY are not evident after subchronic administration for up to 4 weeks.