A comparison of the action of facilitatory and depolarizing drugs at the mammalian motor nerve terminal

Facilitatory and depolarizing drugs both produce facilitation of the cat skeletal muscle, and antidromic firing in the motor nerve following an orthodromic stimulus. Drugs were administered i.v. or close-arterially to the anterior tibialis muscle of the cat, and gross motor nerve potentials were recorded from the ventral root. Antidromic firing following an orthodromic stimulus was asychronous in the presence of facilitatory drugs and a mixture of synchronous and asynchronous firing in the presence of depolarizing drugs. The depolarizing drugs and the facilitatory drugs, neostigmine, edrophonium and ambenonium, also produced antidromic firing in the absence of nerve stimulation. Methoxyambenonium augmented the antidromic firing of the depolarizing drugs following an orthodromic stimulus but prevented it in the absence of nerve stimulation. Hemicholinium and triethylcholine prevented the antidromic firing produced by both facilitatory and depolarizing drugs. Tubocurarine also prevented the antidromic firing by both types of drug. The results are explained on the basis of two cholinoceptive sites on the motor nerve terminal, one at the first node and the other on the unmyelinated terminal.