The pharmacological actions of polymethylene bistrimethyl-ammonium salts.

Since the classical work of Crum Brown and Fraser, the curariform action of many onium salts has been recognized, and other activities exerted by these compounds have been described, such as those commonly called nicotine-like or muscarine-like. In the present paper an account is given of the actions of members of a polymethylene bistrimethylammonium series, whose general formula is (CH,), N+(CH,),, N+(CH,),.21. The compounds will be referred to by the value of n ; thus C10 is the decane derivative, where n=10. Our attention was drawn to the series during a test of the power of the octamethylene compound to liberate histamine. After the injection of a small dose into a cat, there was no depressor response, such as histamine-liberators cause (MacIntosh and Paton, 1949); on the contrary, the blood pressure rose. This rise was evidently asphyxial, since the respiration had simultaneously ceased ; but there were no gasps or convulsive movements such as usually accompany asphyxia, and the sequence of events suggested some form of neuromuscular block. This series has also been independently studied by Barlow and Ing, with whom a simultaneous preliminary report was arranged (Barlow and Ing, 1948a ; Paton and Zaimis, 1948a), and who have now reported their results more fully (Barlow and Tng, 1948b). Following a further note (Paton and Zaimis, 1948b), preliminary clinical trials of the decane derivative as a substitute for d-tubocurarine chloride in anaesthesia and convulsion therapy were instituted. These have proved successful, and the name ‘‘ decamethonium iodide ” has been approved by the British Pharmacopoeia Commission as the official name for the compound. Our investigations of the pharmacological actions of these compounds have been chiefly directed to studying their activity in blocking neuromuscular transmission. Particular attention * Brltlsh Council scholar. has been paid also to describing how the pharmacological activity varies with the length of the polymethylene chain. Later papers will report more fully experiments on other pharmacological actions.