Your browser doesn't support javascript.
loading
Knowledge-Based Design of Long-Chain Arylpiperazine Derivatives Targeting Multiple Serotonin Receptors as Potential Candidates for Treatment of Autism Spectrum Disorder.
Lacivita, Enza; Niso, Mauro; Mastromarino, Margherita; Garcia Silva, Andrea; Resch, Cibell; Zeug, Andre; Loza, María I; Castro, Marián; Ponimaskin, Evgeni; Leopoldo, Marcello.
Affiliation
  • Lacivita E; Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via Orabona, 4, 70125 Bari, Italy.
  • Niso M; Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via Orabona, 4, 70125 Bari, Italy.
  • Mastromarino M; Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via Orabona, 4, 70125 Bari, Italy.
  • Garcia Silva A; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS). Universidade de Santiago de Compostela. Avda. de Barcelona, s/n, 15782 Santiago de Compostela, Spain.
  • Resch C; Cellular Neurophysiology, Hannover Medical School, 30625 Hannover, Germany.
  • Zeug A; Cellular Neurophysiology, Hannover Medical School, 30625 Hannover, Germany.
  • Loza MI; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS). Universidade de Santiago de Compostela. Avda. de Barcelona, s/n, 15782 Santiago de Compostela, Spain.
  • Castro M; Center for Research in Molecular Medicine and Chronic Diseases (CIMUS). Universidade de Santiago de Compostela. Avda. de Barcelona, s/n, 15782 Santiago de Compostela, Spain.
  • Ponimaskin E; Cellular Neurophysiology, Hannover Medical School, 30625 Hannover, Germany.
  • Leopoldo M; Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, via Orabona, 4, 70125 Bari, Italy.
ACS Chem Neurosci ; 12(8): 1313-1327, 2021 04 21.
Article in En | MEDLINE | ID: mdl-33792287
Autism spectrum disorder (ASD) includes a group of neurodevelopmental disorders characterized by core symptoms such as impaired social interaction and communication, repetitive and stereotyped behaviors, and restricted interests. To date, there are no effective treatments for these core symptoms. Several studies have shown that the brain serotonin (5-HT) neurotransmission system is altered in both ASD patients and animal models of the disease. Multiple pieces of evidence suggest that targeting 5-HT receptors may treat the core symptoms of ASD and associated intellectual disabilities. In fact, stimulation of the 5-HT1A receptor reduces repetitive and restricted behaviors; blockade of the 5-HT2A receptor reduces both learning deficits and repetitive behavior, and activation of the 5-HT7 receptor improves cognitive performances and reduces repetitive behavior. On such a basis, we have designed novel arylpiperazine derivatives pursuing unprecedently reported activity profiles: dual 5-HT7/5-HT1A receptor agonist properties and mixed 5-HT7 agonist/5-HT1A agonist/5-HT2A antagonist properties. Seventeen new compounds were synthesized and tested in radioligand binding assay at the target receptors. We have identified the dual 5-HT1AR/5-HT7R agonists 8c and 29 and the mixed 5-HT1AR agonist/5-HT7R agonist/5-HT2AR antagonist 20b. These compounds are metabolically stable in vitro and have suitable central nervous system druglike properties.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autism Spectrum Disorder Limits: Animals / Humans Language: En Journal: ACS Chem Neurosci Year: 2021 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autism Spectrum Disorder Limits: Animals / Humans Language: En Journal: ACS Chem Neurosci Year: 2021 Document type: Article