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At our Research Unit we are especially interested in drugs which have no local epileptogenic effect (at whatever concentration they are directly applied to whatever group of neurons) but produce a generalized epileptic seizure when they are injected in large doses, while in smaller doses they cause a more or less acute diminution of cortical electrogenesis, secondary to hypoxia (toxic, hypoglycaemic, etc.). Of these agents we have studied insulin, ammonium salts (see the next report, I ) and some local anaesthetics.The convulsant action of insulin was studied in particular by Waltregny and Mesdjian ( 3 , 4 ) who demonstrated that this agent produces signs of hypoglycaemic hypoxia when it lowers the blood sugar level by about one-third, but gives rise to electro-clinical and EEG changes of generalized epileptic seizures when it lowers the blood sugar to 40 or 35 mg/100 ml. The same authors subsequently demonstrated that, when EEG signs of generalized epilepsy appear as a result of insulin injection, the convulsive threshold as estimated by the metrazol (pentetrazol) test is lowered considerably.This paper intends to supplement the studies of Waltregny and Mesdjian (3, 4) by presenting an appraisal of the effect of insulin injection and the resulting hypoglycaemia on an epileptic focus provoked in cats by cortical application of penicillin or tungsten paste. MATERIAL AND METHODWe used 20 cats in chronic experiments, because in acute experiments on cats immobilized with flaxedil (gallamine triethiodide) there is secretion of adrenalin, which neutralizes the effect of the insulin (Sutter and Mialhe, 2).Epilepsia, 9 (1968) 311-316

SUMMARY This study was focused on the intravenous injection of ammonium chloride in man and in animals. Both in man and in animals, rapid injection of a dose of 3–8 mg/kg body weight produced a burst of symmetrical, bilaterally synchronous slow waves without any significant change in heart rate, arterial pressure or respiration. Larger doses produced the same slow waves in the EEG, followed by a flattening of the EEG associated with clinical evidence of convulsive movements. Cats given even larger doses (up to 100 mg/kg) showed the abovementioned EEG changes followed by generalized discharges of spikes, spike‐and‐waves, multiple spikes and multiple‐spikes‐and‐waves, either isolated or in bursts, often in association with massive myoclonic jerks identical to those produced by pentetrazol injection and some‐ times leading to a grand ma1 seizure. Direct application of ammonium chloride to the cortex, however, never caused epileptic manifestations but merely produced lasting local suppression of electrogenesis. Les auteurs se sont particuliàerement intëressës A ľinjection intra‐veineuse de chlorure ďammonium chez ľhomme et chez ľanimal. The study thus disclosed two different effects of ammonium chloride: effects rem‐ iniscent of transient cerebral anoxia (small doses), and generalized epileptic mani‐ festations (doses larger than are ever used in man). Résumé Ľinjection rapide ďune dose comprise entre 3 et 8 mg/kg provoque chez ľhomme et chez ľanimal une bouffée ďondes lentes bilathales, synchrones et symëtriques sans modifications importantes du rythme cardiaque, de la tension artérielle et de la respiration. Des quantités plus importantes provoquent les mêmes anomalies lentes électroencéphalographiques suivies ďun aplatissement des tracés accompagés, du point de vue clinique, de mouvements convulsifs. A des doses beaucoup plus fortes allant jusqu'àa 100 mg/kg chez ľanimal (chat) ľaplatissement observé précedemment est suivi de décharges généralisées de pointes, pointes ondes, polypointes et polypointes ondes soit isolées, soit groupées en bouffées souvent associées àa des myoclonies massives identiques àa celles produites par injection de cardiazol et susceptibles ďaboutir àa une crise grand mal. Par contre ľapplication directe du chlorure ďammonium sur le cortex n'a jamais provoqué de manifestations épileptiques mais seulement une dépression locale et durable de ľélectrogénàese. Les auteurs ont donc mis en évidence deux effets diffirénts du chlorure ďammonium: àa faible dose, des effets trés évocateurs ďune anoxie cérébrale transitoire; àa forte dose, jamais utilisée chez ľhomme, des manifestations épileptiques généralisées.

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