Abstract
Major depression is one of the most common psychiatric disorders, and therapeutics for treatment have been in development for decades. The majority of antidepressants prescribed are selective serotonin reuptake inhibitors (SSRIs), but a 4-6 week delay of antidepressant effects is common, a dangerous wait time for patients struggling with depression. Coadministration of a 5-HT1A agonist with an SSRI has been shown to decrease this delay time significantly, but the current library of agonists lacks a drug with both high affinity and selectivity. High affinity correlates to high efficacy, and high selectivity potentially correlates to low chances of side effects. This work proposes modifications to the market drug BMY 7378 to increase binding affinity while maintaining selectivity. The library will be screened using molecular model docking studies to identify the most promising molecules to be synthesized.
- Students will be trained in the use of docking and molecular modelling software
- Students will independently complete computational docking studies of the proposed library
- Students will analyze the resulting data to determine binding strength and specificity
- Students are encouraged to propose additional targets based on docking trends
Once a small set of promising molecules are identified, organic synthesis of the molecules can begin, at which point students will be trained in appropriate methods for sythesis and purification.