EPILEPTIC PHENOMENA INDUCED IN THE CAT BY THE ANTI-DEPRESSANTS MAPROTILINE, IMIPRAMINE, CLOMIPRAMINE, AND AMITRIPTYLINE

  • 1 January 1979
    • journal article
    • research article
    • Vol. 14  (3) , 485-497
Abstract
The epileptogenic properties of 4 tricyclic antidepressant drugs (maprotiline, imipramine, clomipramine and amitriptyline), were investigated in locally anesthetized cats immobilized with gallamine and supplied with neocortical, hippocampal, and reticular recording electrodes. The drugs were infused i.v. 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 4 antidepressants produced local signs of epileptiform pathology. Generalized sustained discharges occurred, on the average, at between 20 and 25 mg/kg with all 4 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. Climipramine 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 3 being norepinephrine and serotonin uptake inhibitors, induced a high amplitude sleep pattern. Maprotiline, a norepinephrine uptake inhibitor which may be devoid of serotonin-uptake inhibiting properties, led to high amplitude slow waves only with doses of at least 12.5-15 mg/kg.

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