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The epileptogenic properties of four tricyclic antidepressant drugs: maprotiline, imipramine, clomipramine, amitriptyline, were investigated in locally anesthetized cats immobilized with gallamine and supplied with neocortical, hippocampal, and reticular recording electrodes. The drugs were infused intravenously at a constant rate (0.5 or, in some cases, 0.25 mg/kg per min) up to a final dose of 45 mg/kg. Already in small doses (1 to 5 mg/kg) all four antidepressants produced local signs of epileptiform pathology. Generalized sustained discharges occurred, on the average, at between 20 and 25 mg/kg with all four drugs. Imipramine and amitriptyline, after the first or first few generalized discharges, led to a pattern of repeated short generalized seizures alternating with silent periods. Maprotiline invariably produced this later alternating pattern only after a 10- to 30-min period of a seminormal high amplitude pattern. Clomipramine assumed a position between maprotiline on the one hand and imipramine and amitriptyline on the other. Starting at doses of 2-4 mg/kg, imipramine, clomipramine and amitriptyline, all three being norepinephrine and serotonin uptake inhibitors, induced a high amplitude "sleep" pattern. Maprotiline, a norepinephrine uptake inhibitor, which is thought devoid of serotonin-uptake inhibiting properties, led to high amplitude slow waves only with doses of at least 12.5 to 15 mg/kg. |
