Abstract
The effects of various curare-like compounds on the contractile responses to carbachol and suxamethonium of thin strips of chick biventer cervicis and of leech muscle have been studied. In chick muscle, suxamethonium and carbachol appeared to act on the same receptor, and were antagonized by tubocurarine, gallamine, and three substituted decamethonium derivatives. The actions of tubocurarine and gallamine, deviated only very slightly from the conventional competitive model; in contrast, the decamethonium derivatives exhibited a qualitatively different kind of antagonism. Experiments with these compounds, including a 2-chloroethylamine derivative that caused an irreversible type of block, showed that the degree of antagonism produced was increased if the antagonist was applied at the same time as, or shortly after, a dose of agonist. This was confirmed in experiments with leech muscle, in which suxamethonium and carbachol appeared to act on different receptors; the substitute decamethonium compounds showed specificity for the suxamethonium receptors, and here the same kind of interaction with agonist as had been seen with chick muscle was observed. It is postulated that agonists cause a change in the molecular structure of the receptor that increases the affinity of the receptor for certain antagonists. This has been termed the metaphilic effect, and it is suggested that this molecular change may be related to the processes of stimulation and desensitization by agonists.
ACKNOWLEDGMENT We are extremely grateful to Dr. E. W. Gill for preparing the drugs DPC10, DNC10, and DPC20M especially for the purposes of this study.
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