5-HT3 Receptor Ligands and Their Effect on Psychomotor Stimulants

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.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Medicinal Chemistry

Year dc:date.available

2008

Author dc:creator

• Worsham, Jessica Nicole

• m-chlorophenylguanidine
• Chemicals and Drugs
• Medicine and Health Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/1054

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-2053