Boosting Synaptic Transmission with Pyridine and Nicotinamide Derivatives

This collaborative initiative investigates novel pyridine-based compounds designed to enhance synaptic transmission and develop advanced neurological therapies.

Project Summary

In the proposed project, our team aims to investigate the use of newly synthesized compounds based on pyridine and nicotinamide structures (3-hydroxy-2-pyridines and derivatives of vitamins B6 and B3) as bioactive agents in modulating neurotransmission.

We will determine the cytotoxicity, myotoxicity, and genotoxicity of the tested compounds to eliminate those with potential adverse effects and reduce the costs of future preclinical studies. Using the obtained results, we will conduct a structure-activity relationship analysis and, by applying a medicinal chemistry approach, predict new compounds with improved efficacy, selectivity, and safety profiles. Through this multidisciplinary approach, we will gain a comprehensive picture of our compounds' activity across three interconnected neurotransmission systems—cholinergic, glutamatergic, and serotonergic—and draw conclusions regarding their potential as drugs for modulating neurotransmission.

Objectives

First objective

Assesment of the compounds’ potential to serve as agonists or antagonists at key signal-transduction receptors involved in fast-synaptic neurotransmission (nicotinic acetylcholine receptor (nAChR), N-methyl-D-aspartate receptors (NMDAR) or a-amino-3-hydroxy-5-methylisoxazolepropionic acid receptor (AMPAR) and 5-hydroxytryptamine receptors (5-HT3).

Second objective

Assesment of the compounds’ ability to inhibit monoamine oxidase (MAO-A and MAO-B), enzymes critical for the breakdown of neurotransmitters such as serotonin, noradrenaline, and adrenaline.

Third objective

Exploration of the compounds’ potential to cross blood-brain barrier and act in the central nervous system.

Our Team

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News

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Contact

Institute for Medical Research and Occupational Health

Ksaverska cesta 2, 10000 Zagreb

+385 (1) 4682 500

www.imi.hr