Electronic Theses and Dissertations

Date of Award


Document Type


Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Bonnie A. Avery

Second Advisor

Christopher R. Mccurdy

Third Advisor

Soumyajit Majumdar

Relational Format



Considering the alarming rates at which substance drug abuse, especially cocaine, is increasing in today's society, there is a lot of impetus on the development of medications that can effectively help alleviate its toxicity and addiction. The affinity of cocaine to sigma receptors (sigma-1 and sigma-2) rendered the hypothesis that blocking sigma receptors could be a possible mechanism to attenuate cocaine-induced toxicity and addiction. In this view, SN79, a synthetic compound with selectivity to both sigma-1 and sigma-2 receptors garnered our attraction for its use as an antagonist. This dissertation encompasses detailed investigation of SN79 from drug discovery and development perspective. Development and validation of a bio-analytical method using ultra performance liquid chromatography-mass spectrophotometry to selectively separate and identify SN79 in biological matrix was a crucial part of this project. Determination of various physicochemical parameters including aqueous solubility, chemical stability, Log P and pKa etc are presented. A number of in vitro tests necessary for predicting the compound's profile in the body were also performed. Single dose pharmacokinetic studies were conducted in fasted and fed state rats that help determine the disposition of SN79 in vivo.





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