title: Potential serotonergic agents for the treatment of schizophrenia.
abstract: BACKGROUND
  For the last 30 years, drugs targeting serotonin receptors (5-HTR) have been intensively investigated in schizophrenia. New drugs targeting 5-HTRs are under development in patients with schizophrenia.
  
  
  METHODS
  In this review, the authors describe the recent clinical trials for schizophrenia with selective serotonergic agents and provide an opinion on how the investigated drugs can help to fulfil current treatment needs. Clinical trials were found in US and EU clinical trial registries and in the medical literature. Relevant 5-HTR antagonists active in animal models of schizophrenia were also analysed.
  
  
  CONCLUSIONS
  Antipsychotics reduce positive symptoms of schizophrenia (delusions, hallucinations and disordered thought), but have undesirable side effects. Moreover, satisfactory treatment of negative symptoms (apathy, poverty of speech, lack of interest in social interactions) and cognitive dysfunction is currently not available. The selective 5-HT2CR full agonist vabicaserin showed antipsychotic efficacy with fewer side effects than olanzapine. Adjunctive pimavanserin (a selective 5-HT2AR inverse agonist) facilitated antipsychotic dose and side-effect reductions. Selective 5-HT3R antagonists (ondansetron, tropisetron and granisetron) showed positive results on negative symptoms and/or cognitive impairments in phase II trials. Adjunctive ondansetron has now entered a phase III trial for such indications. Finally, 5-HTA5R and 5-HT7R antagonists have shown procognitive actions in animal models of schizophrenia. These novel serotonergic drugs seem promising for improving the current treatment of schizophrenia.
authors.affiliation: a Pharmacology & Therapeutics , Craven , Villemoisson-sur-Orge , France.
authors.forename: Ricardo P
authors.initials: RP
authors.lastname: Garay
authors.affiliation: b Neurobiology of Anxiety and Depression, School of Medicine , University of Nantes , Nantes , France.
authors.forename: Michel
authors.initials: M
authors.lastname: Bourin
authors.affiliation: a Pharmacology & Therapeutics , Craven , Villemoisson-sur-Orge , France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: de Paillette
authors.affiliation: c Centre Médico-Psychologique B, CHU Clermont-Ferrand, EA 7280 , Clermont-Ferrand University , Clermont-Ferrand , France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Samalin
authors.affiliation: a Pharmacology & Therapeutics , Craven , Villemoisson-sur-Orge , France.
authors.forename: Ahcène
authors.initials: A
authors.lastname: Hameg
authors.affiliation: c Centre Médico-Psychologique B, CHU Clermont-Ferrand, EA 7280 , Clermont-Ferrand University , Clermont-Ferrand , France.
authors.forename: Pierre-Michel
authors.initials: PM
authors.lastname: Llorca
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D018490:Serotonin Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D015507:Drugs, Investigational; D018490:Serotonin Agents
keywords: 5-HT receptor antagonists; Serotonin; clinical trials; schizophrenia; serotonin receptor antagonists