Description:

Background

Serotonin (5-hydroxytryptamine, 5-HT) plays a critical role in the etiology of numerous central and peripheral nervous system disorders. Currently, 14 different subtypes of 5-HT receptors have been identified out of which 5‑HT7 and 5‑HT1 have shown involvement in disorders including migraine headaches, depression, and autism. Research suggests simultaneous activation of these subtypes may lead to unwanted side effects reducing the efficacy of the treatment. Hence, there is a need for the activation of select subtypes. 

With modifications of previously known ligands, researchers have discovered several 5-HT7-moderately selective, 5-HT1A-selective, and dual 5-HT7/5-HT1A receptor ligands that could be used to advance the pathophysiological and pharmacotherapeutic understanding of 5-HT7 and 5-HT1A receptors. 

Technology Overview

In this invention, Northeastern University researchers propose the synthesis of novel 5-SAT analogs to develop a 3-dimensional quantitative structure affinity relationship (3D-QSAR) at the human 5-HT7 receptor for comparison with similar studies at the highly homologous 5-HT1A receptor. This will help in understanding the structural differences between the receptors and better modulate their activity. The affinity, stereo-selectivity, and receptor selectivity of new ligands have been proved by 3D-QSAR and in-silico models. This invention puts forward novel, efficacious, and safe 5-SAT chemotypes for the treatment of neurodevelopmental and neuropsychiatric disorders. 

Benefits

  • Compounds with high affinity and selectivity 
  • Selective modulation of 5-HT1 or 5-HT7
  • Dual targeting 
  • High blood-brain barrier penetration 
  • Reduced side effects 

Applications

  • With further studies, ligands can be clinically translated for the treatment of 
    • Neurodevelopmental disorders such as autism, dyslexia 
    • Neuropsychiatric disorders including psychosis, addictions, repetitive behaviors, anxiety 
    • Fragile X syndrome 
    • Gastrointestinal disorders 
    • Management of withdrawal symptom of opioid, cannabis 

Opportunity

  • License
  • Partnering
  • Research collaboration
Patent Information:
Category(s):
Drug Discovery
Chemistry
For Information, Contact:
Mark Saulich
Associate Director of Commercialization
Northeastern University
m.saulich@northeastern.edu
Inventors:
Raymond Booth
Keywords:
autism
drug abuse, gastrointestinal disorders