The pharmacological actions of polymethylene bistrimethylammonium salts / by W.D.M. Paton and Eleanor J. Zaimis.

  • William Paton
Date:
[1949?]
Catalogue details

Licence: In copyright

Credit: The pharmacological actions of polymethylene bistrimethylammonium salts / by W.D.M. Paton and Eleanor J. Zaimis. Source: Wellcome Collection.

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    Rabbit 3. Not killed. Alive and well 1 year later. C6. Rabbit 1. Normal. Rabbit 2. Scanty focal patches of infiltration of meninges by lymphocytic cells. No other abnor¬ mality. Rabbit 3. (Killed 4 months after last injection of C6.) The pia arachnoid contains an obvious excess of round cells of lymphocytic type, and similar cells accompany many of the penetrating vessels (cf. Rabbit 2). Fairly common areas of perivascular infiltration occur deeply and irregularly within the brain sub¬ stance. Several foci of neuroglial proliferation are found in the cerebral hemispheres, unrelated to blood vessels, to recent destructive lesions, or to anatomical structures. Their significance is quite obscure. No other abnormality. Antibacterial action Although there was no reason to suppose that this series of compounds possessed an important antibacterial action, it seemed of interest to deter¬ mine how far this activity varies with the length of the polymethylene chain. We are much indebted to Dr. A. T. Fuller for testing them for us. Table XII gives the concentrations of the various TABLE XII Inhibitory concentration of polymethylene bistrimethyl- ammonium salts in mg./100 ml. (parts per 100,000). Compound Streptococci Staphylococci B. coli C2 500 >500 >500 C3 500 >1,000 >1,000 C4 1,000 >1,000 >1,000 C5 500 >1,000 >1,000 C6 500 >1,000 >1,000 Cl 500 -j > 1,000 >1,000 C8 750 >1,000 >1,000 C9 500 1,000 >1,000 CIO 300, 300 1,000 >1,000 Cll 200 200 >500 C12 150, 100 100, 200 100, 200 C13 50 50 50 C18 0.3 0.8 8 compounds which prevent visible growth in 18 hours at 37° C. of streptococci, staphylococci, and B. coli. The antibacterial activity is negligible from C3 to Cl2, and is only appreciable with Cl8. Even with the latter compound, however, the activity is only of theoretical interest. The surface tension of aqueous solutions of the bistrimethylammonium series The change of pharmacological action with polymethylene chain length among these com¬ pounds clearly raised the question as to how far this might be due to change in the proportion of hydrocarbon chain to polar groups in the mole¬ cule. The measurement of surface tension at an air-water interface provided a suitable method for studying this. Table XIII gives the values obtained TABLE XIII Depression of surface tension of water by polymethyiene bistrimethylammonium salts (concentration 1 mg./c.c.). Compound: C2 C3 C4 C5 C6 C7 C8 C9 C10C11 C12 C13 C18 Ay(dy4es) : 0.4 0.4 0.1 1.3 1.0 1.4 0.6 1.8 1.3 1.3 4.0 4.3 19.3 for the depression of the surface tension of water by members of the series, in solutions containing 1 mg./c.c. of each salt. With most of the com¬ pounds there was little depression of the normal surface tension of the water. With C12 and Cl 3, however, a distinct depression was observed, which became substantial with Cl8. Care was taken to control the time for which the surface was allowed to rest undisturbed before making a measurement, although the gradual fall of tension with time described for many surface-active substances was only observed with solutions of Cl8. The depres¬ sion of tension recorded is therefore to some extent an arbitary one (measured after 10 min. had elapsed from first creating the surface), but it appeared to be within 5-10 per cent of the maxi¬ mum value. It follows from these observations that one cannot look to changes in surface activity to explain variations in pharmacological actions of members below about Cl2. Discussion Species difference One of the most remarkable properties of the members of this series, and especially of CIO, was the very great variation in their activity according to the species of animal on which they were tested. Such a variation is much smaller, and in the reverse sense, with d-tubocurarine chloride. Varia¬ tion of this sort has been described for many other onium salts, but its magnitude for CIO, sufficient to make a compound of great activity in the cat appear to be of slight activity in the rat, possesses few parallels. The species variation in the sensi¬ tivity to histamine is, perhaps, the nearest to it, in that cats are relatively sensitive and mice and rats highly resistant. But this variation in sensi¬ tivity to histamine receives a possible explanation (Emmelin, 1945) in the respective plasma histamine levels of these animals: it is reasonable that those with plasmas rich in histamine should be resistant to it, since even cats can be accommodated to sus¬ tained histaminaemia. No such circulating onium salt has, however, yet been demonstrated, and we
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