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.
When it is found that the reflex action of the cord is greatly diminished or apparently entirely abolished, it must not be at once concluded that this is necessarily due to the direct paralysing action of the drug itself upon the nervous substance of the cord. This may be the case, and is so when methyl-coniine is employed, but it may be due to the indirect action of the drug upon the heart, weakening the circulation, and lessening the function of the cord by interfering with its blood-supply.
In order to ascertain whether this is the case or not, it is usual to take two frogs as nearly alike as possible, to destroy the brain in each, and after waiting until they have recovered from the immediate shock of the operation, to inject into one the drug to be tested, and, at the moment when it stops the beating of the heart, to tie a ligature around the heart of the other. The persistence of reflex action is then tested in the usual manner, and if it is found that it disappears much sooner in the poisoned frog than in the other one in which the heart has been ligatured, it is concluded the drug has paralysed the substance of the cord itself.
The spinal cord is very rapidly paralysed in mammals if the blood-supply to it is stopped. This is readily shown by Stenson's experiment of gently compressing the abdominal aorta in a rabbit with the thumb or finger, so as to arrest the circulation for four or five minutes. On releasing the animal its hinder extremities are found to be paralysed, and this paralysis, though it may be partly due to interference with the blood-supply of the muscles and nerves of the lower extremities themselves, is chiefly due to the arrest of circulation in the spinal cord. The spinal cord in frogs is less rapidly affected, but if the circulation be arrested for half an hour or so symptoms of paralysis usually begin to appear, the time varying, however, with the temperature and other conditions. Indirect paralysis is produced by aconitine, digitalin, and large doses of quinine, which arrest the circulation. It is frequently difficult to decide how far paralysis is due to the action of a drug on the circulation, and how far to its direct action on the spinal cord itself.
Paralysis of reflex movement is produced by a number of substances, some of which produce little or no previous excitement; others, however, markedly increase the excitability of the spinal cord first, and are thus classed as spinal stimulants.