Tetrahydrocarbazole-based serotonin reuptake inhibitor/dopamine D2 partial agonists for the potential treatment of schizophrenia

Bioorg Med Chem Lett. 2009 Oct 1;19(19):5552-5. doi: 10.1016/j.bmcl.2009.08.050. Epub 2009 Aug 15.

Abstract

A 5-fluoro-tetrahydrocarbazole serotonin reuptake inhibitor (SRI) building block was combined with a variety of linkers and dopamine D2 receptor ligands in an attempt to identify potent D2 partial agonist/SRI molecules for treatment of schizophrenia. This approach has the potential to treat a broader range of symptoms compared to existing therapies. Selected compounds in this series demonstrate high affinity for both targets and D2 partial agonism in cell-based and in vivo assays.

MeSH terms

  • Animals
  • Carbazoles / chemical synthesis
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology
  • Disease Models, Animal
  • Dopamine Agonists / chemical synthesis
  • Dopamine Agonists / chemistry*
  • Dopamine Agonists / pharmacology
  • Rats
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Receptors, Dopamine D2 / agonists*
  • Receptors, Dopamine D2 / metabolism
  • Schizophrenia / drug therapy*
  • Selective Serotonin Reuptake Inhibitors / chemical synthesis
  • Selective Serotonin Reuptake Inhibitors / chemistry*
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin 5-HT1 Receptor Antagonists*

Substances

  • Carbazoles
  • Dopamine Agonists
  • Receptors, Dopamine D2
  • Serotonin 5-HT1 Receptor Antagonists
  • Serotonin Uptake Inhibitors
  • Receptor, Serotonin, 5-HT1A