Novel Serotonin Receptor Agonist to Treat Neurological Disease

NU 2018-135

INVENTORS
Karl Scheidt*
Adam Csakai
Herbert Meltzer

SHORT DESCRIPTION

A novel small molecule that selectively targets serotonin 5-HT2c receptors for the treatment of psychiatric, mental, and/or neurological diseases.

BACKGROUND

Serotonin is a neurotransmitter known to regulate a variety of neurological functions, and alterations in serotonin signaling are linked to several disease states, including cognitive impairment, obsessive compulsive disorder (OCD), and addiction. Serotonin receptors, otherwise referred to as 5-hydroxytryptamine receptors or 5-HT receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems. The 5-HT-2 family includes three members: 5-HT_2a, 5-HT_2b, and 5-HT_2c. Numerous ligands for these receptors’ activity and downstream effects have been developed synthetically or discovered in nature, but these often lack selectivity.  

ABSTRACT

This invention discloses a series of novel beta-carboline-based small molecules designed as positive allosteric modulators of the 5-HT2 receptor, with selectivity for 5-HT2c. The molecules are synthesized with a substituted beta-carboline core that can be modified to achieve the desired saturation and pharmacologic profile, offering a targeted strategy to modulate 5-HT2c receptor signaling while minimizing off-target interactions. These compounds demonstrate promising agonist-like activity in vivo, reducing behaviors associated with schizophrenia, cognitive impairment, OCD, and addiction.

APPLICATIONS

• Therapeutic targeting 5-HT2c for a range of neurological disorders and diseases (ex. Schizophrenia, cognitive impairment, OCD and addiction)

ADVANTAGES

• Selectively targets 5-HT2c receptors over other serotonin receptors
• Treats diseases that currently have few effective treatment options on the market

IP STATUS
Issued US patent US 11,485,734

PUBLICATIONS

Orr M et al. (2022) Discovery of Highly Potent Serotonin 5-HT2 Receptor Agonists Inspired by Heteroyohimbine Natural Products. ACS Med. Chem. Letters. 13: 648-657.

Rajagopal et al. (2023). NU-1223, a simplified analog of alstonine, with 5-HT2cR agonist-like activity, rescues memory deficit and positive and negative symptoms in subchronic phencyclidine mouse model of schizophrenia. Behavioural Brain Research. 454: 114614.