Pyridostigmine bromide was administered subcutaneously in mice, in a dose of 4.0 or 2.0 mu moles/kg, and the activity of the predominant (G1, G4 and A12) molecular forms of acetylcholinesterase were examined in diaphragm, extensor digitorum longus (EDL), and soleus muscles at 3 h, 6 h, 24 h and 5 days. 2. In diaphragm, no effect was apparent after the low dose, but after the high dose there was a reduction in activity of the functional A12 form at 24 h, followed by an increase which had overshot the control level at 5 days. 3. In the fast EDL, after the low dose, all three molecular forms were decreased at 3 h but had returned to normal by 6 h. This effect was not apparent after the high dose. 4. In the slow soleus the low dose caused a significant increase in total enzyme activity at 5 days, but the high dose caused significant increases in all molecular forms at 3 hours. 5. Thus pyridostigmine had delayed effects on the levels of acetylcholinesterase. The three muscles displayed different sensitivities to the drug, but the changes were consistent with initial inhibition of the activity leading to down-regulation of the enzyme followed by up-regulation, which could overshoot the normal levels.
