1In anaesthetized cats, stimulation of the vagus nerves produced bradycardia and a bronchoconstriction which was measured as an increase in lung resistance (RL) and a fall in dynamic lung compliance (Cdyn); these effects were abolished by atropine.2 Gallamine potentiated vagally-mediated changes in RL and Cdyn at doses that blocked muscarinic receptors in the heart and inhibited neuromuscular transmission. (+ )-Tubocurarine and suxamethonium did not affect the response of the lung or the heart to vagal stimulation. 3 Bronchoconstriction induced by intravenous acetylcholine was not potentiated by gallamine, indicating that postsynaptic muscarinic receptors in the lung and changes in muscle tone were not involved. 4 Potentiation of vagally-induced bronchoconstriction appears to be due to blockade of inhibitory muscarinic receptors located in the pulmonary parasympathetic nerves innervating both central and peripheral airways. 5 Pilocarpine was an agonist for these neuronal receptors as it inhibited vagally-induced bronchoconstriction at low doses (lO ng to 1 pg kg-).6 The results demonstrate that gallamine is an antagonist and pilocarpine an agonist at neuronal muscarinic receptors which attenuate parasympathetic nerve activity in feline lung.

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.

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Summary The effects of edrophonium have been observed in the transversely cut tenuissimus muscle of the cat. Concentrations of edrophonium 10−7M to 10−5M increased the amplitude of the end‐plate potential (e.p.p.) but produced no greater increase in time course than previously observed in curarized muscle. When the e.p.p. and gross nerve action potential were recorded simultaneously, antidromic discharges were observed in the motor nerve concomitantly with repetitive e.p.ps in the presence of edrophonium. Edrophonium produced no effect on the input resistance or equilibrium potential of the end‐plate. The fractional release of transmitter was significantly increased by edrophonium but there was no increase in the quantal release of transmitter in the transversely cut muscle preparation. In curarized muscle edrophonium also increased the quantal release, the size of the available store of transmitter and the rate of refilling of the available store. It is concluded that edrophonium facilitates transmission to skeletal muscle by inducing a repetitive antidromic discharge in the nerve, following orthodromic stimulation. The antidromic discharge propagates by axon reflex to other nerve terminals of the same motor unit producing repetitive e.p.ps. It is also suggested that edrophonium antagonizes tubocurarine by acting as a partial agonist at the motor nerve terminal.