This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
Fig. 48. - Tracing of the contraction curve of a muscle poisoned by veratrine, showing enormous prolongation of the contraction, the recording cylinder making many complete revolutions before the muscle is completely relaxed.
This action of veratrine is most marked at moderate temperatures.
It is much diminished, and sometimes entirely removed, by cold; and it disappears also when the temperature of the muscle is considerably raised. When the muscle which has been cooled or heated is again brought back to a moderate temperature, the contracture sometimes returns, but occasionally does not, the effect of veratrine on the muscle appearing to be sometimes, but by no means always, destroyed by the heat or cold to which the muscle has been exposed.1
1 Marey, Travaux du Laboratoire, 1878, p. 157.
2 Mosso, Les Ptomaines, Turin, 1883.
The result of this exceedingly prolonged contraction is that a frog poisoned with veratrine is able to jump with considerable power, but the extensor muscles, by which the movement is executed, remain contracted instead of relaxing. The animal therefore lies extended and stiff, and is only able very slowly to draw its legs up towards the body. After they have been drawn up, the flexors in their turn remain contracted for a while, and so the animal is unable to jump until some time further has elapsed.
Another remarkable point about the action of veratrine on muscle is, that although a single contraction lasts so long as seriously to interfere with the power of co-ordinated movement, yet, if the muscle is made to contract a few times in rapid succession, the effect of the veratrine disappears, and it again acts normally. After a short rest the effect of veratrine again reappears.
A similar action to that of veratrine is exerted by salts of barium, which, when locally applied, cause the muscle to describe peculiarly elongated curve at a moderate temperature, and its restoration nearly to the normal by cooling and heating.
a curve resembling that of veratrine, not only in its form, but in the alterations produced by temperature and in its temporary disappearance after repeated contractions. A similar action is exerted also, though to a less extent, by strontium and calcium. Salts of potassium may at first increase the height of contraction, but afterwards both moderate and large doses shorten the muscular curve, and lessen its height, so as finally to abolish its contractile power altogether. When applied to a muscle poisoned by veratrine, barium, strontium, or calcium, salts of potassium remove the excessive prolongation of the contraction which these drugs occasion, and restore the muscular curve again to its normal.1
Fig. 49. - Tracing of the contraction curves of a muscle poisoned by veratrine, showing the
1 Brunton and Cash, Journ. of Physiol, vol. iv. p. 1, and Centralblatt f.d. med. Wiss., 1883, No. 6.
Although veratrine alters the form of the muscular curve so greatly, it does not (excepting in large doses) paralyse the muscle, so that when a poisoned muscle is made to contract at regular intervals for a length of time, it is able to do as much work as a normal one.
Nearly allied to this is another group of muscular poisons, some of which have already been mentioned as a sub-division of Group I. It contains: digitalin, digitalein, digitaleresin, digitoxin, toxiresin, scillain, helleborein, oleandrin, adonidin, neriodorin, and neriodorein. Tanghinia, thevetin, and frynin, or toad poison, probably also belong to this class.
These drugs do not lessen the irritability of muscle, but appear to alter somewhat the form of the muscle curve, somewhat in the same way, but to a less extent than substances of the veratrine group. Some of them when applied in a concentrated form directly to the muscle cause a condition of rigor. This is especially the case with caffeine and digitalin. This rigor is well marked in the rana temporaria, and only to a comparatively slight extent in the rana esculenta. Although caffeine in concentrated solution produces rigor mortis in the muscle, yet in very dilute solutions it is a muscular stimulant, and as such is included in the sixth group.
Group V. contains physostigmine, which increases the excitability of muscle to slight stimuli, but does not increase the amount of work it can do; on the contrary, in large doses it diminishes it.
Poisons belonging to this group in small doses increase muscular work, and cause the muscle to recover rapidly after exhaustion. Creatin has this power to a great extent; hypoxanthin has it also, though less powerfully. The effect of these substances is very interesting, because they are products of muscular waste. They also occur in beef-tea, and their action appears to show that beef-tea assists muscular power, as well as acts as a nervous stimulant.
Other members of this group are caffeine and glycogen : these have great power to increase muscular work. The relation of caffeine to hypoxanthin is very interesting. Xanthin, which is another substance derived from muscles, differs from hypoxanthin in containing one atom more oxygen. Theobromine, the active principle of cocoa, is dimethylxanthine; and caffeine, the active principle of tea and coffee, is trimethylxanthine. The restorative effects of beef-tea, coffee, tea, and cocoa have long been recognised empirically, although their action could not be explained. It now seems not at all improbable that it may be partly due to their restorative effect on the muscle.
1 Brunton and Cash, Proc. Roy. Soc, 1883.