Effect of repeated treatment with pyridostigmine on acetylcholinesterase in mouse muscles.

1. Pyridostigmine bromide was administered subcutaneously (0.4 mumoles/kg) in mice twice a day for 3 weeks. The activities of the predominant (G1, G4 and A12) molecular forms of acetylcholinesterase were determined in diaphragm, extensor digitorum longus (EDL) and soleus muscles. 2. After the treatment the G4 and A12 forms were reduced in diaphragm, but increased in EDL and soleus. One week later all forms were elevated in all three muscles. At 2 weeks the activity had returned to normal in diaphragm but not in EDL and soleus. 3. A single dose of pyridostigmine was administered in mice which had been pretreated for 3 weeks and left untreated for 2 weeks, and in control mice. 4. In the controls there was no significant effect on the enzyme activities in diaphragm up to 5 days, but there were decreases in EDL, and increases in soleus. In the pretreated group all three forms were increased in diaphragm, especially the A12 form. In soleus and EDL there was a prolonged decrease in all forms, although in the soleus the A12 activity remained above normal. 5. Repeated treatment with pyridostigmine caused delayed changes in functional acetylcholinesterase. Furthermore the treatment had altered the sensitivity of the muscles to the drug.