The prejunctional actions of some non-depolarizing blocking drugs

1. Trains of end-plate potentials (e.p.p.s) have been recorded from the isolated tenuissimus of the cat. The muscle was paralyzed either by transversely cutting the muscle fibres or by non-depolarizing blocking drugs.2. The following parameters of transmitter synthesis, storage and release have been calculated: the quantal content of the first e.p.p. in the train, the size of the available store, fractional release, quantum size, and the rate of refilling of the available store.3. Tubocurarine and benzoquinonium depressed the rate of refilling of the available store causing its depletion at high rates of stimulation. This was offset by an increase in fractional release, which in the case of tubocurarine was sufficient for the quantal content of the first e.p.p. to be unchanged.4. Dimethyltubocurarine and pancuronium had a similar effect to tubocurarine on the rate of refilling of the store and depletion of the store at high rates of stimulation but did not increase fractional release. There was, therefore, a decrease in the quantal content of the first e.p.p.5. Lignocaine depressed the rate of refilling of the store and depleted the store at high rates of stimulation. Fractional release was also depressed.6. It is suggested that the non-depolarizing drugs have a weak local anaesthetic action retarding the influx of sodium into the nerve terminal which slows the rate of refilling of the store. This effect is due to the quaternary ammonium head. The presence of a phenolic group increases fractional release due either to an increased influx of calcium into the nerve terminal or to a potentiation of the actions of calcium.