Paralysis of autonomic ganglia by methonium salts / by W.D.M. Paton and E.J. Zaimis.

  • Paton, William D. M.
Date:
[1951?]
Catalogue details

Licence: In copyright

Credit: Paralysis of autonomic ganglia by methonium salts / by W.D.M. Paton and E.J. Zaimis. Source: Wellcome Collection.

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    PARALYSIS OF AUTONOMIC GANGLIA BY METHONIUM SALTS BY W. D. M. PATON AND E. J. ZAIMIS From the National Institute for Medical Research, Mill Hill, London, N.W.l (Received December 18, 1950) The production of ganglionic block by the lower members of the polymethylene bistrimethylammonium series was briefly described in earlier papers (Paton and Zaimis, 1948, 1949a, b). The experiments, which are now reported in full, were designed to analyse the mechanism by which these compounds paralyse autonomic function and to determine how far such ganglionic blockade accounts for the pharmacological properties of the drugs. We have found that the compounds interfere with transmission only at the synapse itself, that they cause block without any previous excitation, and that they do not interfere with the release of acetyl¬ choline in the ganglion. Further, they are free from other pharmacological actions, in particular from curare-like, muscarine-like, or histamine-liberating activity. They constitute, indeed, the most specific ganglionic inhibitors so far described. Certain members (the butane, pentane, and hexane derivatives) have been submitted to clinical trial, and have received the approved names of tetramethonium, pentamethonium, and hexamethonium respectively. These names will be used in this paper; the other members of the series will be referred to by the number of carbon atoms in the polymethylene chain. Methods Cats anaesthetized with chloralose (80 mg./kg.) were used for most experiments. In experiments on the superior cervical ganglion, the contractions of the nictitating membrane were recorded on a smoked drum. These contractions were evoked by the application of maximal “ square-wave ” electrical stimuli, of 0.5 msec, duration, to the cut peripheral stump of the cervical sympathetic, divided and separated from the vagus in the neck, or to the postganglionic trunk after dissection of the ganglion. Perfusion of the ganglion was by the technique of Kibjakow (1933) and Feldberg and Gaddum (1934), the perfusion fluid being warmed to the cat’s body temperature by its passage through a tube passed into the stomach of the cat and emerging from a small cut in the oesophagus, close to the ganglion (Macintosh, 1949). The perfusion fluid was Locke’s solution containing 5 x 10 b eserine. The acetylcholine in the perfusate was assayed on the blood-pressure of an eviscerate, eserinized cat. Cat’s blood-pressure was recorded in the usual way by means of a siliconed cannula containing a little 1 per cent heparin, inserted into the carotid artery. For studying the effects of vagal stimulation, the left or right vagus nerve was divided in the neck, and the peripheral end was separated from the sympathetic and excited electrically. To record intestinal activity in the cat, a length of small intestine, about 6 cm. long, was selected and glass cannulae inserted at each end, tying them in by ligatures round the submucosa only; after the intestine