The pharmacology of the toxiferines / by W.D.M. Paton and W.L.M. Perry.

  • William Paton
Date:
[1951?]
Catalogue details

Licence: In copyright

Credit: The pharmacology of the toxiferines / by W.D.M. Paton and W.L.M. Perry. Source: Wellcome Collection.

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    preparation: decamethonium, on the other hand, potentiates the effects of acetyl¬ choline on this preparation, and itself produces a contracture. This experiment provides a simple and crucial test for analysing the nature of the neuromuscular block produced by toxiferines. The addition of a few micrograms of a toxiferine to the bath containing the frog rectus preparation produced a definite antagonism to acetylcholine, and there was no sign that the toxiferine itself could cause a con¬ tracture. The antagonism was measured quantitatively as follows: Several contrac¬ tions to the same dose of acetylcholine were recorded ; then toxiferine was added to the bath, and this reduced the acetylcholine response ; the amount of acetyl¬ choline necessary, in the presence of the toxiferine, to restore the response to the original size was then determined. Thus, if the original dose of acetylcholine must be trebled during toxiferine paralysis in order to produce the original effect, then two-thirds of this acetylcholine have been antagonized ; i.e., there is 67 per cent inhibition. Fig. 3 gives the dosage-response lines relating the concentration of toxiferine in the bath with the percentage inhibition of acetylcholine calculated on this basis, and shows that toxiferine XI is more potent than toxiferines I and VI. pA2 (Schild, 1947) is the negative logarithm of the concentration of an antagonist which causes 50 per cent inhibition of some effect, and we have indicated it by a dotted line in Fig. 3. The single point determined for toxiferine VI corresponds exactly with a similar point for toxiferine I. The pA2 for all three compounds thus lies between 8 and 9. This value is comparable with that of atropine against the action of acetylcholine on the guinea-pig’s ileum (8.27 ; Schild, 1947) and illustrates quantitatively their extremely high activity. Effect on respiratory muscles.—The respiratory muscles have a particularly high sensitivity to the toxiferines. Fig. 4 compares the effect of toxiferine I on the cat’s tibialis with its effect on the minute volume of the same cat. A dose of 9 /xg./kg. of toxiferine I produced a depression of the minute volume of some 5-10 per cent, without in any way affecting the tibialis twitch. The dose was then increased by the injection of 14 /xg./ kg., which, allowing for partial elimination of the previous dose. Fig. 4.—Cat, chloralose. Lower record, tibialis; nerve shocks every 10 sec. Upper record, graph of respiration. Intravenous injections. At (a) toxiferine I, 9 ^g./kg.; at (b) toxiferine I, 14 /xg./kg.; and at (c) artificial respiration started. increased the total dose to about 20 /xg./kg., with the result that the respiratory movements were depressed to such an extent as to require the application of artificial respiration ; the blocking of the tibialis muscle was of the order of 40 per cent only. The original 5-10 per cent effect on the respiration was accompanied by a rise in blood-pressure, presumably asphyxial in origin. Similar results were obtained with
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