On the Anticonvulsive Effect of Quinidine I. Experimental investigation of somatomotor, vegetative and bioelectrical aspects of convulsive seizures elicited by electroshocks

SUMMARY 1 In 61 non-anaesthesized cats the action of a 1% quinidine sulphate solution was studied, observing the clinical and vasomotor aspect of crises induced by transcerebral electroshock. In curarized cats the cortical and thalamic electroencephalographical aspects of these crises were studied. 2 Intravenous administration of 10–17.5 mg/kg quinidine stops the electrical consulsive crises and, more frequently even, the transformation of its aspect from tonic to clonic (with the same parameters of stimulation as in the crisis test), and leads to the disappearance of the arterial hypertension, which accompanies the tonic epileptic crises. 3 The anticonvulsive action of quinidine sulphate is not due to the arterial hypotension produced by the drug, for the correction of the hypotension by means of adrenalin does not impede the anti-epileptic action of quinidine sulphate. Moreover, other experiments have shown that the clinical and vasomotor aspect of the epileptic crises is not a function of the arterial pressure. 4 A dosage of 7–10 mg/kg i.v., of quinidine results in a flattening of the curves in the EEG, immediately after the administration. Waves of 6 or 11 c/sec and with a large amplitude, which alternate with periods of no electrical phenomena are observed. This resembles more or less the preparation of the “isolated brain”. At these dosages the curves resume their normal aspect after 4–5 minutes. 5 Higher dosages of up to 30–40 mg/kg cause a considerable bradycardia and at the same time an almost complete disappearance of cortical and thalamic EEG-waves, on which the ECG is superposed. This aspect is reversible after 10–15 minutes, however. 6 Dosages of 10–12.5 mg/kg markedly reduce the electrical crisis, both in voltage and duration. Dosages of up to 30 mg/kg lead to the disappearance of the cortical crisis, whereas epileptic discharges are still present in the thalamic leads, though they are considerably reduced. 7 The neuraxial niveau of the action of quinidine is especially discussed. RESUME 1 On a etudie sur 61 chats non-anesthesies l'action du sulphate de quinidine (sol. 1%) en recherchant l'aspect clinique et vasomoteur des crises induites par electro-choc transcerebral, aussi bien que, chez le chat curarise, l'aspect electroencephalographique, cortical et thalamique, des memes crises. 2 L'administration par voie intraveineuse de 10–17.5 mg/kg de quinidine determine la suppression de la crise electroconvulsive, ou bien, plus frequemment, la transformation de son aspect tonique en clonique (aux memes parametres de stimulation que la crise test), ainsi que la disparition de l'hypertension arterielle qui accompagne les crises epileptiques toniques. 3 L'action anticonvulsivante du sulphate de quinidine n'est pas determinee par l'hypotension arterielle provoquee par le drogue, car sa correction avec l'adrenaline n'empeche pas son action antiepileptique; de meme, d'autres preuves experimentales ont montre que l'aspect clinique et vasomoteur de la crise epileptique n'est pas en concordance avec le niveau de la pression arterielle. 4 La quinidine (7–10 mg/kg, i.v.) agit sur l'EEG en determinant, immediatement apres l'administration, un aplatissement du trace, avec l'apparition des bouffees de 6 c/sec ou de 11 c/sec, de grande amplitude, alternant avec des periodes de silence electrique, ce qui rappelle dans une certaine mesure la preparation du „cerveau isole”. A ces doses, le trace revient a son aspect normal apres 4–5 minutes. 5 Des quantites plus grandes, allant jusqu'a 30–40 mg/kg, determinent une bradycardie importante et, parallelement, un silence electrique cortical et thalamique presque total, sur lequel se superpose l'ECG. Cet aspect est quand meme reversible apres 10–15 minutes. 6 Les doses de 10–12.5 mg/kg reduisent beaucoup la crise electrique, en tant que voltage et duree. Des doses allant jusqu'a 30 mg/kg font disparaitre la crise corticale, tandis que les derivations thalamiques continuent a presenter des decharges epileptiques, quoique beaucoup plus reduites. 7 On discute surtout le niveau nevraxiel d'action quinidinique.