Abstract
Electroencephalographic (EEG) effects of maprotiline, a new antidepressant, were compared with those of imipramine and amitriptyline in conscious rabbits with chronically implanted electrodes. All drugs were dissolved in isotonic saline and administered i.v.. Maprotiline (5, 10 mg/kg) induced a drowsy EEG pattern, i.e. high voltage slow waves in the cortex and desynchronization of hippocampal theta waves. Imipramine (1, 2, 5 mg/kg) and amitriptyline (1, 2, 5 mg/kg) also elicited similar EEG effects but were more potent than maprotiline in this respect. Maprotiline (5, 10 mg/kg) failed to suppress the EEG arousal responses induced not only by auditory stimulation but also by electrical stimulation of the centromedian thalamus, posterior hypothalamus and mesencephalic reticular formation, whereas imipramine (2, 5 mg/kg) and amitriptyline (1, 2, 5 mg/kg) inhibited these responses. The EEG arousal response induced by i.v. injection of physostigmine 0.1 mg/kg showed little change after maprotiline (5, 10 mg/kg), while the response was significantly suppressed by imipramine (2, 5 mg/kg) and amitriptyline (1, 2 mg/kg). Maprotiline (5, 10 mg/kg) had no effect on the recruiting response induced by electrical stimulation (8 Hz) of the centromedian thalamus and enhanced the limbic after-discharges elicited by hippocampal or amygdaloid stimulation, while imipramine (2, 5 mg/kg) and amitriptyline (1, 2, 5 mg/kg) caused an initial depression followed by sustained enhancement of these after-discharges. These results demonstrate maprotiline to be an anti-depressant of a new type which has no effect on the ascending reticular activating system and a slight central anticholinergic action.
