Brain 5-HT1C receptors and antidepressants

Prog Neuropsychopharmacol Biol Psychiatry. 1994 May;18(3):563-74. doi: 10.1016/0278-5846(94)90013-2.


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, oxaprotiline) and two atypical antidepressants (mianserin and trazodone) were found to display affinity for 5-HT1C receptors in the nanomolar range. 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-HT1C receptors, except fluoxetine. When tested in an in vivo functional model revealing agonistic or antagonistic properties at 5-HT1C receptors, all antidepressants displaying high affinity for this receptor type (except fluoxetine, clomipramine, trimipramine and oxaprotiline) were antagonists at 5-HT1C receptors. Antidepressants with lower 5-HT1C receptor affinity (except nomifensine) were inactive in this functional in vivo model. Antagonism at brain 5-HT1C receptors is a component of the antiserotonergic properties of a number of established antidepressants, especially of the tricyclic class.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents, Tricyclic / pharmacology
  • Dopamine / metabolism
  • In Vitro Techniques
  • Ligands
  • Male
  • Neurotransmitter Uptake Inhibitors / pharmacology
  • Penile Erection / drug effects
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin Antagonists


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Ligands
  • Neurotransmitter Uptake Inhibitors
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Dopamine