Brain 5-HT 1C receptors and antidepressants

Abstract

1. A variety of antidepressants of different chemical classes were tested for their in vivo and in vitro activity at 5-HT 1C receptors in the brain. 2. Conventional tricyclic antidepressants (imipramine, desipramine, maprotiline, clomipramine, trimipramine, amitriptyline, nortriptyline, doxepin, amoxapine, oxaprotiline) and two atypical antidepressants (mianserin and trazodone) were found to display affinity for 5-HT 1C receptors in the nanomolar range. 3. Antidepressants of other chemical classes and mechanisms of action (serotonin uptake inhibitors: fluoxetine, citalopram, sertraline, fluvoxamine; noradrenaline dopamine uptake inhibitors: nomifensine, bupropion, amineptine; or monoamine oxidase inhibitors: moclobemide, iproniazid) had affinities in the micromolar range for 5-HT 1C receptors, except fluoxetine. 4. When tested in an in vivo functional model revealing agonistic or antagonistic properties at 5-HT 1C receptors, all antidepressants displaying high affinity for this receptor type (except fluoxetine, clomipramine, trimipramine and oxaprotiline) were antagonists at 5-HT 1C receptors. Antidepressants with lower 5-HT 1C receptor affinity (except nomifensine) were inactive in this functional in vivo model. 5. Antagonism at brain 5-HT 1C receptors is a component of the antiserotonergic properties of a number of established antidepressants, especially of the tricyclic class.