Certain drugs when administered to animals or taken by man produce convulsions. The muscular actions which occur in these convulsive movements may be induced by (a) irritation of the motor centres in the spinal cord, (b) the motor centres in the medulla oblongata and pons Varolii, or (c) cerebral cortex. These centres may be irritated directly by the action of the drug upon them, or they may be stimulated indirectly by the drug causing the blood in them to become venous through its action on the respiratory or circulatory organs. Convulsions of this sort, although caused by the administration of a poison, are really asphyxial, and are similar in character to those produced by suffocation.

Convulsions are usually ascertained to be of spinal origin by dividing the cord either at the occiput or lower down in its course and finding that they still persist in those parts of the body which derive their innervation from the spinal cord below the point of section. If they cease in parts of the body innervated by the spinal cord alone, but continue in the parts which retain their nervous connection with the brain, they are regarded as of cerebral origin (v. p. 179).

It has already been mentioned that irritation of the motor areas in the cortex of the brain will produce epileptic convulsions, but it is probable that such cortical irritation acts through lower ganglionic centres and especially through the medulla oblongata and pons Varolii. Epileptic convulsions can be still more readily produced by irritation of this part of the brain than by irritation of the cerebral cortex, and may be induced by a slight lesion of the pons and medulla by a needle. It is to irritation of this part of the brain by venous blood that asphyxial convulsions are due, for they can still be induced by suffocation or by ligature or compression of all the arteries leading to the brain after all the parts of the brain above the pons have been removed, and they cease when the spinal cord is divided just below the medulla, or the medulla itself divided at its lower end. It is evident that, if the spinal cord be paralysed, the convulsions will not occur though the medulla and pons be irritated; and it has been found that, if its blood-supply is stopped at the same time as the circulation in the pons by ligaturing the aorta in place of the cerebral vessels alone, convulsions do not occur. Probably the absence of convulsions in slow asphyxia is due, at least in some degree, to gradual paralysis of the cord by the long-continued circulation of venous blood through it.

1 Francois-Franck and Pitres, op. cit.

The centre for convulsions in the frog appears to be in the medulla oblongata.

Asphyxial convulsions are usually of an opisthotonic character, because, all the muscles being stimulated at once by the action of the venous blood on the motor centres, the stronger overpower the weaker, and the extensor muscles of the back being more powerful than the flexors bend the spine backwards. Asphyxial convulsions only occur in warm-blooded animals and not in frogs, where the respiratory processes are slow, and entire stoppage of the respiration for a length of time does not render the blood sufficiently venous to act as a powerful irritant. If any drug therefore produces convulsions in the higher animals and not in frogs, the probability is that its convulsive action is indirect and the convulsions it produces are asphyxial. If, on the other hand, it produces convulsions in frogs as well as higher animals, its convulsive action is in all probability due to the direct effect of the drug upon the nerve-centres. In order to ascertain this definitely, however, the usual plan is to see (1) whether the convulsions which occur after the drug has been injected disappear when artificial respiration is commenced, and (2) whether these convulsions are prevented by artificial respiration begun before the injection of the drug and kept up during its action. But even this does not entirely show whether the convulsive action of a drug is direct or indirect, for artificial respiration will not prevent asphyxial convulsions if these should depend upon the action of the drug in stopping the heart and thus arresting the circulation. If it is found that the convulsions occur very shortly after the heart stops, the usual plan is to paralyse the vagus in the heart by atropine, and ascertain whether the convulsive action then occurs. If the drug still produces convulsions when respiration is kept up and the heart is not stopped, it is almost certain that its action is direct upon the nerve-centres.

Experiments to ascertain whether convulsions are asphyxial or not may be conveniently made upon fowls, for the venous or arterial condition of the blood is readily ascertained by the colour of the comb. Thus, in fowls killed by cobra poison, the convulsions come on at the moment the comb becomes livid, and when artificial respiration is begun the convulsions disappear as the comb again regains its normal colour. It is evident that the colour of the comb will indicate the condition of the blood supplying the brain, even though a venous condition of it should be due to stoppage of the heart and not to failure of the circulation.

Camphor has a curious exciting action both upon the brain and upon the medulla. It produces first rapid succession of ideas, great desire to move, hallucinations which are generally agreeable, and a wish to dance and laugh. In animals it has a similar action, causing wild excitement and constant motion, succeeded by clonic epileptiform convulsions, during which death often occurs. Usually, if they survive the convulsions, they recover; but in man the convulsive stage may be succeeded by paralysis, coma, and death, the parts of the nervous system which are first excited being apparently finally paralysed. The action upon frogs is different from that on warm-blooded animals, for in them it produces such rapid paralysis both of the spinal and motor nerves that convulsions do not occur.

Among other drugs having a powerful convulsant action due to irritation either of the cortical centres or of the medulla and pons are picrotoxin (the active principle of Anamirta cocculus or Cocculus indicus), cicutoxine (the active principle of Cicutavirosa), and the active principle of the nearly-allied (Enanthe crocata, coriamyrtin (from Coriaria myrtifolia), digitaliresin and toxiresin, which are products of the decomposition of the active principles of digitalis.

The method of localising the parts of the brain upon which certain drugs exert a convulsant action, consists in extirpating some of the motor centres and then giving these drugs, such as picrotoxin, cinchonidine, and quinine,1 which produce epileptic convulsions.2 The results of these experiments are that the epileptic convulsions produced by these poisons appear to have a twofold origin, (a) in the brain, and (b) in the medulla, the centre in the brain being the most sensitive to the action of the poison. In consequence of this, when the poison is given after the destruction of the motor centres on one side in such quantities as not to cause general convulsions, the weakness of the opposite side, due to the lesions, becomes still more evident, probably from the motor excitability of the sound side being increased. When convulsions are produced they are unsymmetrical. Those of the sound side are much stronger, are generally clonic, and apparently arise from irritation of the cerebral centres. Those of the paralysed side are much weaker, are more tonic, and apparently arise from irritation of the medulla.

1 I have seen a case in which an epileptic convulsion appeared to be caused by medicinal doses of quinine.

2 Rovighi e Santini, Publicazioni del R. Instit. di stud. superiori in Firenze. Sezione di scienze fisiche natur. 1882, s. 1.