QF2004B, a potential antipsychotic butyrophenone derivative with similar pharmacological properties to clozapine

Neuropharmacology. 2006 Aug;51(2):251-62. doi: 10.1016/j.neuropharm.2006.03.021. Epub 2006 May 11.


The aim of the present work was to characterize a lead compound displaying relevant multi-target interactions, and with an in vivo behavioral profile predictive of atypical antipsychotic activity. Synthesis, molecular modeling and in vitro and in vivo pharmacological studies were carried out for 2-[4-(6-fluorobenzisoxazol-3-yl)piperidinyl]methyl-1,2,3,4-tetrahydro-carbazol-4-one (QF2004B), a conformationally constrained butyrophenone analogue. This compound showed a multi-receptor profile with affinities similar to those of clozapine for serotonin (5-HT2A, 5-HT1A, and 5-HT2C), dopamine (D1, D2, D3 and D4), alpha-adrenergic (alpha1, alpha2), muscarinic (M1, M2) and histamine H1 receptors. In addition, QF2004B mirrored the antipsychotic activity and atypical profile of clozapine in a broad battery of in vivo tests including locomotor activity (ED50 = 1.19 mg/kg), apomorphine-induced stereotypies (ED50 = 0.75 mg/kg), catalepsy (ED50 = 2.13 mg/kg), apomorphine- and DOI (2,5-dimethoxy-4-iodoamphetamine)-induced prepulse inhibition (PPI) tests. These results point to QF2004B as a new lead compound with a relevant multi-receptor interaction profile for the discovery and development of new antipsychotics.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Butyrophenones / pharmacology*
  • CHO Cells
  • Carbazoles / pharmacology*
  • Catalepsy / drug therapy
  • Clozapine / pharmacology*
  • Cricetinae
  • Cricetulus
  • Humans
  • In Vitro Techniques
  • Isoxazoles / pharmacology*
  • Male
  • Mice
  • Models, Molecular
  • Motor Activity / drug effects
  • Radioligand Assay
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Dopamine / metabolism
  • Receptors, Histamine H1 / metabolism
  • Receptors, Muscarinic / metabolism
  • Receptors, Serotonin / metabolism
  • Reflex, Startle / drug effects
  • Stereotyped Behavior / drug effects


  • Antipsychotic Agents
  • Butyrophenones
  • Carbazoles
  • Isoxazoles
  • QF 2004B
  • Receptors, Adrenergic, alpha
  • Receptors, Dopamine
  • Receptors, Histamine H1
  • Receptors, Muscarinic
  • Receptors, Serotonin
  • Clozapine