Interaction of benzilylcholine mustard, benzilylcholine and lachesine with the histamine receptor in the longitudinal muscle of guinea-pig ileum

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Abstract
1 The histamine receptors of longitudinal muscle strips from guinea-pig ileum were inactivated on extended exposure to concentrations of benzilylcholine mustard (BCM) above 10−6M. These concentrations are 3 orders of magnitude greater than those required for inactivation of the muscarinic receptors. Mepyramine (3 × 10−8M) afforded complete protection for the histamine receptor against the effects of BCM. 2 Recovery from block at 30° C was very slow with a first-order rate constant of approximately 10−7 s−1. 3 The rate constant, k2, for the alkylation reaction in which the reversible BCM-receptor complex is converted into an irreversible complex is much greater than the rate constant, k–1, for dissociation of the reversible complex. The value of the rate constant, k1, for formation of the reversible complex was 1·1 ± 0·2 × 103 M−1 s−1. 4 These observations suggested that k1 was probably not much greater than for BCM acting on the muscarinic receptor, even though the value of k1 was reduced by more than 2 orders of magnitude. This effect has been established for benzilylcholine and lachesine, reversible analogues of BCM. For both drugs k1 for the histamine receptor was approximately 3 orders of magnitude less than for the muscarinic receptor, whereas k-1 was greater by a factor of only 6.

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