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.
Curare produces symptoms of paralysis. Paralysis may be due to the action of the drug on the muscles themselves, on the motor nerves which set them in action, or on the nerve-centres which originate motor impulses. In order to decide this, Bernard applied electricity to the nerves and to the muscles of a frog poisoned by curare administered subcutaneously. He thus found that when the nerve was irritated no effect was produced on the muscles; but that when the muscle itself was stimulated, it contracted readily. In order to decide whether this loss of irritability in the nerve was due to a change in the nerve-trunk, or in the terminations within the muscle, Bernard employed the first method, that of local application. He placed a solution of curare in two watch-glasses. In one he immersed the trunk of the nerve (Fig.
Fig. 52. - Shows the method of applying a drug in solution locally to the trunk of a nerve.
52), and in the other the muscle, so that the solution penetrating between the fibres could reach the nerve-endings (Fig. 53). He of motor nerves within it.
Fig. 53 - Shows the method of applying a drug in solution locally to a muscle and the ends then irritated the nerve attached to both muscles, and found that irritation caused contraction readily enough in the case where the nerve-trunk had been steeped in the solution of curare, but had no effect when the curare had been allowed to reach the nerve-ends by immersion of the muscle in the solution. The irritability of the muscle itself to mechanical stimuli, or to the making and breaking of a constant current directly applied to it, remained quite unaltered, so that the muscular fibre had evidently not been affected by the action of the poison.
The second mode of testing the action of drugs upon motor nerves, viz. that of local protection, consists, as has been stated, in allowing the drug to be carried to the muscles and nerve-endings by the circulating blood in one leg of a frog, while it is prevented from reaching the other either by ligaturing (Fig. 54) the bloodvessels alone, or ligaturing the whole leg with the exception of the sciatic nerve. After some time has elapsed, the sciatic nerve is stimulated on each side. If the muscles of the poisoned limb do not contract at all or do so more feebly than in the unpoisoned limb, it is evident that the poison has paralysed either them or the motor nerves. In order to decide whether the nerves or the muscles are paralysed the muscle is next stimulated directly; if it then contracts normally it is evident that the paralysis observed when the nerve was irritated is due to the action of the drug on the nerve-endings. If the muscle is completely paralysed, no definite conclusion can be drawn regarding the nerve-endings, but if the muscle shows only partial paralysis, and the paralysis is greater when the nerve is stimulated than when the muscle is stimulated directly, we conclude that the drug has acted upon both the muscular substance itself and the motor nerve-endings within it.
Fig. 54. - Diagram of the mode of experimenting on motor and sensory nerves in the frog. - The-shaded part shows where the poison has been carried by the circulation. The unshaded left leg shows where the tissues have been protected from the poison by ligature of the artery just above the knee. The unbroken lines with arrows pointing to the spinal cord indicate the sensory nerves. The broken line with arrows pointing outwards indicates the motor nerve to-the unpoisoned leg.
The effect of drugs in paralysing motor nerves is chiefly investigated in frogs as the action comes out much more distinctly in them.
Warm-blooded animals may die from paralysis of the motor nerves while the nerves still respond readily to faradaic stimuli applied to them, the faradaic stimulus being much greater than that normally sent along the nerves from the nerve-centres. Thus after an animal has been killed by paralysing it with curare, its muscles will still respond readily to electrical stimulation of the motor nerves.
A fallacy to be guarded against in experiments on the results of preventing a poison from reaching one part of the body is that caused by diffusion. Even when the circulation is stopped in a frog's leg by ligature of the artery, poison introduced into the dorsal lymph-sac may pass down the limb by diffusion and affect the parts below the ligature. This may be to a great extent prevented by ligaturing the whole limb en masse, at the same time carefully excluding the sciatic nerve from the ligature. Diffusion may also occur although the circulation has been stopped throughout the whole body by removal of the heart and other viscera, and the anterior part of the spinal cord may be affected before the posterior when the poison is injected into the dorsal lymph-sac.