Carbonic anhydrase activators. The selective serotonin reuptake inhibitors fluoxetine, sertraline and citalopram are strong activators of Isozymes I and II

A Casini, S Caccia, A Scozzafava, CT Supuran*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

18 Citations (Scopus)

Abstract

The selective serotonin reuptake inhibitors (SSRI) fluoxetine, sertraline and citaloprant have been investigated for their ability to activate two carbonic anhydrase (CA) isozymes, hCA I and hCA II, in parallel with two standard activators for which the X-ray structure (in complex with isozyme II) has been resolved: histamine and phenylalanine. All three SSRI activated both isozymes with potencies comparable to that of the standards although the profile was different: for hCA 1, best activators were fluoxetine and histamine, with citalopram and sertraline showing weaker activity. For hCA II, the best activators were phenylalanine and citalopram, and the weakest histamine and sertraline, whereas fluoxetine showed an intermediate behavior. These results suggest that SSRI efficacy in major depression complicating Alzheimer's disease may be partly due to their ability to activate CA isozymes and may lead to the development of potent activators for the therapy of diseases associated with significant decreases in brain CA activity. (C) 2003 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)2765-2768
Number of pages4
JournalBioorganic & Medicinal Chemistry Letters
Volume13
Issue number16
DOIs
Publication statusPublished - 18-Aug-2003
Externally publishedYes

Keywords

  • COMPLICATING ALZHEIMERS-DISEASE
  • HIGH-AFFINITY
  • HISTAMINE DERIVATIVES
  • DOUBLE-BLIND
  • ACYL)ETHYL-1H-IMIDAZOLE
  • MOIETIES
  • MEMORY
  • ENHANCEMENT
  • EXPRESSION
  • DEPRESSION

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