IMPROVED THERAPY FOR DEPRESSION

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Depression is a heterogenous disease, covering a range of severity, qualities and causes that affects an important portion of population. None of the available treatment modalities of depression including electroconvulsive therapy and pharmacotherapy mainly by tricyclics and monoamine oxidase inhibitors are totally satisfactory and new drugs are needed. The MAO inhibitors have been underrated mainly due to the undesired side effects but safer new drugs would much expand their use. A possibility to improve the central activity and reduce the peripheral effects of trans (+/-)-phenylcyclopropanamide (tranylcypromine, TCP), one of the few MAO inhibitors still in use is proposed. The application of a dihydropyridine <--> pyridinium salt redox type chemical delivery system (CDS) approach to TCP could represent a good possibility to achieve these goals by enhancing the brain uptake, prolonging duration in the central nervous system and facilitating elimination from periphery. Various type CDS will be synthesized for TCP. In vitro examination including lipophilicity determination and stability in chemical oxidants and in biological matrices as well as preliminary biological activity and toxicity studies will help to select derivatives for further investigation. A properly developed CDS for TCP could improve the therapy of depression.