Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs.

Article Details

Citation

Jenck F, Moreau JL, Mutel V, Martin JR, Haefely WE

Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs.

Eur J Pharmacol. 1993 Feb 9;231(2):223-9. doi: 10.1016/0014-2999(93)90453-o.

PubMed ID
8453978 [ View in PubMed
]
Abstract

A variety of antidepressants of different chemical classes were tested for their in vivo and in vitro activity at 5-HT1C receptors in the brain. Conventional tricyclic antidepressants (imipramine, desipramine, maprotiline, clomipramine, trimipramine, amitriptyline, nortriptyline, doxepin, amoxapine) as well as mianserin and trazodone were found to display high to low nanomolar affinity for 5-HT1C receptors. Antidepressants of other chemical classes and with other mechanisms of action (affecting amine uptake systems: fluoxetine, citalopram, sertraline, fluvoxamine, nomifensine, amineptine; or monoamine oxidase inhibitors: moclobemide, iproniazid) had negligible affinities (micromolar range) for 5-HT1C receptors, except fluoxetine. When tested in an in vivo rat model thought to reveal functional agonistic or antagonistic properties at 5-HT1C receptors, all antidepressants displaying high affinity for this receptor type (except clomipramine and trimipramine) were antagonists at 5-HT1C receptors. Antidepressants with a lower affinity for 5-HT1C receptors (except nomifensine) were inactive in this functional in vivo model. Taken together, these results suggest that antagonism at brain 5-HT1C receptors is a component of the antiserotonergic properties of a number of established antidepressants. In addition, the study confirmed that 5-HT1A receptors functionally interact with 5-HT1C receptors, which suggests that some degree of activity at 5-HT1A receptors may also be an important property for antidepressant activity.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Amitriptyline5-hydroxytryptamine receptor 1AProteinHumans
Unknown
Inhibitor
Inducer
Details
Amitriptyline5-hydroxytryptamine receptor 1CProteinRat
Unknown
Antagonist
Details
Nortriptyline5-hydroxytryptamine receptor 1CProteinRat
Unknown
Antagonist
Details