Defense Date


Document Type


Degree Name

Master of Science


Medicinal Chemistry


Drug abuse and addiction are considered to be a result, at least in part, of the rewarding effects produced by increasing dopamine levels. 5-HT3 serotonin receptors have been shown to indirectly affect dopamine levels. Therefore, the effect of the 5-HT3 receptor partial agonist, MD-354, on the actions of psychomotor stimulants was analyzed in mouse locomotor activity assays to determine whether MD-354 is working through a 5-HT3 receptor agonist or antagonist mode of action. Studies with (+)amphetamine and (+)methamphetamine in combination with MD-354 indicated MD-354 is either devoid of action or is behaving similar to the 5-HT3 receptor antagonist, ondansetron. This effect could be occurring centrally; however peripheral effects can not be discounted. In combination with cocaine, MD-354 behaved similar to the 5-HT3 receptor agonist, SR 57227A, known to act both centrally and peripherally. This difference between central and peripheral effects could account for the different modes of action observed with MD-354. Studies also involved synthesis of potentially brain-penetrant carbamate analogs of MD-354, and QSAR to assist in validating a 5-HT3 receptor agonist pharmacophore.


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Date of Submission

June 2008