Fluvoxamine influences serotonergic system in the brain: neurochemical evidence

The effects of a relatively new antidepressant drug, fluvoxamine, were compared with those produced by chlorimipramine on the 5-hydroxytryptamine system in rat brain. Daily treatment with fluvoxamine (25 mg/kg, i.p.) and an equivalent dose of chlorimipramine (28 mg/kg, i.p.) for 7 days reduced (3H)5-hydroxytryptamine uptake by crude synaptosomes (P2 pellet) of brain to 56 and 45%, respectively, but produced no change in midbrain monoamine oxidase activity. Repeated administration of these drugs significantly decreased tryptophan hydroxylase activity as well as tryptophan level in the midbrain region. The concentration of 5-hydroxyindoleacetic acid also was lowered in several discrete areas of the brain, but no change was seen in the endogenous levels of 5-hydroxytryptamine. Our data suggest that fluvoxamine, like chlorimipramine, is a potent inhibitor of 5-hydroxytryptamine uptake. Unlike tricyclic antidepressants, fluvoxamine does not seem to produce any sedation in animals, which was evidenced by no significant change in spontaneous locomotor activity.