The modes of action of gallamine

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Abstract
The action of gallamine, a classical competitive neuromuscular blocking agent, was examined on voltage-clamped endplates of frog skeletal muscle fibers. Gallamine produces a parallel shift of the equilibrium log (concentration)-response curves in concentrations of up to .apprx. 40 .mu.M. At a membrane potential of -70 mV the Schild plot of the dose ratios so measured has a gradient of slightly less than the theoretical value, for a competitive antagonist, of unity. The apparent equilibrium constant for competitive block is .apprx. 2 .mu.M, and is approximately independent of the membrane potential. Fluctuation analysis of the endplate current shows 2 components in the presence of gallamine. The results can be fitted, over the range tested, by a mechanism that involves block of open ion channels by gallamine in a manner similar to that by procaine or quaternary local anaesthetic analogs. The rate constants for this action are strongly dependent on the membrane potential. At -100 mV the association rate constant is about 4 .times. 107/M per s, the dissociation rate constant is .apprx. 600/s, and the equilibrium constant about 15 .mu.M. Other kinetic measurements (voltage-jump relaxation, and nerve-evoked endplate currents) give results consistent with this conclusion, but apparently these results are valid over a range of conditions narrower than that for fluctuation analysis.

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