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Sedative/anxiolytic effects of antidepressants in animals.


The sedative effects of several different structural types of antidepressants were investigated in mice. Six different models of sedation were used and the results were averaged. The rank order of sedative potency was: amitriptyline greater than mianserin greater than maprotiline greater than imipramine greater than desipramine greater than clomipramine greater than alaproclate greater than zimelidine greater than norzimelidine. Sedative potency of the antidepressants was found to be significantly correlated with their affinity for four different brain amine receptors. The rank order of correlation of sedation with receptor affinity was: histamine (H1) greater than serotonergic greater than muscarinic greater than alpha 1-adrenergic. These findings appear to be associated with clinical side effects observed during treatment with antidepressants. While scant literature is available concerning specific anxiolytic effects of antidepressants, pharmacological evidence for the role of central 5-HT systems in the anxiolytic effect is plentiful. Our preliminary findings show a marked antagonism of isolation-induced aggression by low doses of the specific 5-HT uptake inhibitor, zimelidine, and the 5-HT releasing agent, p-chloramphetamine, thus supporting the hypothetical importance of 5-HT in the pharmacology of anxiolytic agents.

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