Ability of Diisopropylfluorophosphonate (D.F.P.) to Produce Antidromic Activity in Motor Nerves

Abstract

Masland and Wig ton 1 demonstrated antidromic activity in motor nerves, occurring in association with fascicular twitching of the muscles produced by neostigmin (Prostigmin), or by eserin. They concluded that the cholinesterase inhibiting action of these drugs led to an accumulation of acetylcholine, which stimulated the motor nerve at its ending, and initiated antidromic impulses. This work was further extended by Eccles, Katz, and Kuffler. 2 These investigators demonstrated that the antidromic activity observed in the motor nerve sometimes originated in the muscle fibre, and at other times originated in the nerve ending itself.

In view of the development of new anticholinesterase drugs, it was of interest to determine whether the new drugs produce similar antidromic activity. A study similar to that previously reported with neostigmin has therefore been made using diisopropylfluorophosphonate (D.F.P.). The drug was injected intramuscularly or intraperitoneally in cats, in doses of 5 to 10 mg, as a 1% solution in peanut oil. Active fascicular twitching of the muscles was usually observed in about 40 minutes from the time of injection. When the drug was injected intramuscularly, the twitching usually appeared first in the limb into which the drug had been injected. When recording electrodes were applied to the motor nerve roots within the spinal canal under these conditions, antidromic activity was recorded. The activity consisted of repeated bursts of nerve impulses, the impulses occurring in groups of 1 to 20, at frequencies up to 200 second during the bursts. The activity appeared to be identical with that previously reported in connection with the administration of neostigmine. (Fig. 1).

These experiments provide further evidence of the similarity of action of eserine, neostigmine, and D.F.P., and support the view that the effect of these drugs on the neuromuscular system is a result of their common action as cholinesterase inhibitors.