P-40 Development Towards Potential Full Spectrum Bipolar Disorder Drugs

Buller Hall 207

The goal of this research project is to develop full spectrum bipolar disorder drugs; there is currently only one on the market. Our approach here is to create single molecular entities with the capacity to address both the manic and depressive phases of bipolar disorder. This is part of our ongoing work in which valproate, a known antimanic agent, is covalently linked to amines known and regularly used as antidepressants. We synthesize these compounds utilizing a one-flask, three-step reaction sequence involving acyl chloride formation, then electrophilic carbonyl addition followed by nucleophilic substitution. Our hybrid quaternary ammonium acylals contain both the valproate and the antidepressant tertiary amines. Currently, the antidepressants amines under study are amitriptyline, imipramine and diphenhydramine, the latter being the antidepressant found in Benadryl. Our bioassaying protocol involves measuring the inositol concentrations of human cell lines upon independent exposure and treatment with (a) our synthesized hybrid compounds, (b) mixtures of valproate and antidepressant, and (c) valproate and antidepressant controls. The cell lines are lymphoblasts obtained from patients diagnosed with bipolar disorders I and II and unaffected individuals.