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LABELLED DECAMETHONIUM IN CAT MUSCLE

1 Tritium‐labelled decamethonium was infused intravenously in 12 cats at final rates of 1.3–4.2 nmol kg−1 min−1 to produce a steady plasma concentration which ranged between 0.21‐1.3 μmol/1 in different experiments. Muscle contractions were elicited by nerve stimulation and the potential at the end‐plate regions of superficial fibres was recorded by extracellular electrodes. 2 Under these conditions, it was not possible to obtain a steady degree of neuromuscular block. The initial decrease in muscle contractions was followed by recovery towards the original value although the concentration of decamethonium in the plasma remained constant, or in some cases rose. The initial depolarization of the end‐plate region also waned during the constant infusion of the drug. 3 Once the twitch tension had returned to control values during infusion of the drug, prolongation of the infusion for a total of four hours did not produce a secondary neuromuscular block. 4 Scintillation counting showed that during infusion of labelled decamethonium the radioactivity of the muscles increased progressively with time. The uptake was less in the soleus muscle than in the fast‐contracting flexor longus digitorum and extensor longus digitorum muscles. Muscles which had been denervated 12–13 days previously showed a greater uptake of labelled drug than control muscles from the contralateral limb. 5 The labelled drug was localized by autoradiography of frozen sections of leg muscles following intra‐arterial injection of decamethonium. Grain counts in individual fibres showed that small amounts of decamethonium had entered the muscle fibres along their entire length, and there was increased uptake of the drug into the cell in the region of the end‐plate. 6 The mechanisms underlying the waning of the pharmacological response during constant application of depolarizing drugs are discussed.