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Effect of chlorimipramine and maprotiline on experimental anxiety in humans

Department of Pharmacology Campus of the University of São Paulo, BR 14049, Ribeirão Preto, SP, Brazil

A.W. Zuardi

Departmtent of Neuropsychiatry Campus of the University of São Paulo, BR 14049, Ribeirão Preto, SP, Brazil

F.G. Graeff

FMRP and Laboratory of Psychobiology Campus of the University of São Paulo, BR 14049, Ribeirão Preto, SP, Brazil

In order to assess the role played by serotonin (5-HT) and noradrenaline in anxiety, four groups of healthy volunteers were given 25 mg of the selective inhibitor of 5-HT uptake chlorimipramine, 50 mg of the selective inhibitor of noradrenaline uptake maprotiline, 1 mg of the benzodiazepine anxiolytic lorazepam or placebo, and submitted to a simulated public speaking (SPS) test, consisting of speaking in front of a videocamera. Subjective anxiety was evaluated by the visual analog mood scale (VAMS) of Norris as well as by the state-trait anxiety inventory (STAI) of Spielberger. Chlorimipramine enhanced SPS-induced anxiety, whereas maprotiline and lorazepam reduced anxiety during as well as outside the test period. Mental and physical sedation (VAMS) were increased by either maprotiline or lorazepam. In a scale of bodily symptoms, chlorimipramine tended to increase muscle tension, agitation and palpitation, whereas maprotiline caused lethargy. The rise in blood pressure induced by the SPS procedure outlasted the period of stress in the group treated with chlorimipramine. In contrast, the SPS-induced increase in heart rate was enhanced by lorazepam. Chlor imipramine and maprotiline reduced salivation to the same extent. Pupillary diameter, however, was significantly increased by chlorimipramine alone. It may be tentatively sug gested that the proanxiogenic effect of chlorimipramine is related to changes in central 5-HT neurotransmission while the anxiolytic effect of maprotiline is associated with alteration of noradrenergic mechanisms. Increased peripheral sympathetic tone may also contribute to the proanxiety action of chlorimipramine.

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