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

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.

[1]  J. Young,et al.  Determination of the number of muscarinic receptors in chick amnion muscle. , 1973, British journal of pharmacology.

[2]  A. Burgen,et al.  Homologues of benzilylcholine mustard , 1972, The Journal of pharmacy and pharmacology.

[3]  M. Hirst,et al.  The conversion of methyl-2-acetoxyethyl-2'-chloroethylamine to an acetylcholine-like aziridinium ion and its action on the isolated guinea pig ileum. , 1972, Canadian journal of physiology and pharmacology.

[4]  J. Stubbins,et al.  A comparison of the action of acetylcholine and acetylcholine mustard (chloroethylmethylaminoethyl acetate) on muscarinic and nicotinic receptors. , 1972, The Journal of pharmacology and experimental therapeutics.

[5]  J. Young,et al.  Labelling of cholinergic receptors in subcellular fractions from rat cerebral cortex. , 1972, Biochemical Journal.

[6]  A. Burgen,et al.  Kinetics of complex formation between human carbonic anhydrases and aromatic sulfonamides. , 1970, Biochemistry.

[7]  A. Burgen,et al.  The action of acetylcholine and other drugs on the efflux of potassium and rubidium from smooth muscle of the guinea‐pig intestine , 1997, British Journal of Pharmacology.

[8]  C. Thron,et al.  The rate of action of atropine. , 1968, The Journal of pharmacology and experimental therapeutics.

[9]  H. Rang THE UPTAKE OF ATROPINE AND RELATED COMPOUNDS BY SMOOTH MUSCLE , 1967 .

[10]  H. Rang,et al.  An alkylating derivative of benzilylcholine with specific and long-lasting parasympatholytic activity. , 1966, Molecular pharmacology.

[11]  H. Rang The kinetics of action of acetylcholine antagonists in smooth muscle , 1966, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[12]  H. Rang STIMULANT ACTIONS OF VOLATILE ANAESTHETICS ON SMOOTH MUSCLE. , 1964, British journal of pharmacology and chemotherapy.

[13]  R. Kitz,et al.  Esters of methanesulfonic acid as irreversible inhibitors of acetylcholinesterase. , 1962, The Journal of biological chemistry.

[14]  W. Paton,et al.  A theory of drug action based on the rate of drug-receptor combination , 1961, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[15]  M. Nickerson Receptor Occupancy and Tissue Response , 1956, Nature.

[16]  H. R. Ing,et al.  11. Synthetic mydriatics , 1947 .

[17]  H. R. Ing,et al.  Synthetic mydriatics. , 1947, Journal of the Chemical Society.