Psychopharmacology

, Volume 126, Issue 3, pp 234–240 | Cite as

Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2C receptor

  • E. -P. Pälvimäki
  • H. Majasuo
  • A. Laakso
  • M. Kuoppamäki
  • E. Syvälahti
  • B. L. Roth
  • J. Hietala
Original Investigation

Abstract

Interactions of the selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine and its main metabolite norfluoxetine, and the tricyclic anti-depressant (TCA) imipramine with the rat serotonin 5-HT2C receptor in a clonal cell line and in the rat choroid plexus were investigated by radioligand binding and phosphoinositide (PI) hydrolysis assays. For comparison, the affinities of a variety of other antidepressants of different chemical classes for the cloned rat 5-HT2C and 5-HT2A receptors were also determined by radioligand binding assays. Fluoxetine displayed relatively high affinity for the 5-HT2C receptor in the choroid plexus, with a Ki value for inhibition of [3H]mesulergine binding of 55.4 nM. The Ki values for imipramine, norfluoxetine and citalopram were 136 nM, 203 nM, and 298 nM, respectively. Similar rank order of potency was detected in PI hydrolysis assays, which showed that these drugs are antagonists at the 5-HT2C receptor without exhibiting inverse agonist activity. [3H]Ketanserin (5-HT2A) binding assays revealed that the SSRIs fluoxetine, norfluoxetine and citalopram show 10- to 23-fold selectivity for the 5-HT2C receptor in vitro, whereas the TCA imipramine does not. Many other TCAs also had high to intermediate affinity for both 5-HT2A and 5-HT2C receptors. The present data provide evidence that fluoxetine, norfluoxetine and citalopram, along with many other antidepressant compounds, interact directly with the 5-HT2C receptor.

Key words

Citalopram Fluoxetine Imipramine Antidepressants Serotonin 5-HT2C receptor Serotonin 5-HT2A receptor 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • E. -P. Pälvimäki
    • 1
  • H. Majasuo
    • 1
  • A. Laakso
    • 1
  • M. Kuoppamäki
    • 1
  • E. Syvälahti
    • 1
  • B. L. Roth
    • 2
  • J. Hietala
    • 3
  1. 1.Department of Pharmacology and Clinical Pharmacology, Institute of BiomedicineUniversity of TurkuTurkuFinland
  2. 2.Departments of Psychiatry and Biochemistry, School of MedicineCase Western Reserve UniversityClevelandUSA
  3. 3.Department of PsychiatryTurku University Central HospitalTurkuFinland

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