Dual Mechanism Analgesia-Enhancing Agents

Currently, there is an increasing need for novel analgesics that are potent but lack undesired side effects. Recent studies have shown that both 5-HT3 receptors and α2B- adrenoceptors play a role in antinociception. MD-354, N-(3-chlorophenyl)guanidine, has a high-affinity both for 5-HT3 and α2B- adrenoceptors and could be viewed as the first example of a rather selective 5-HT3/α2B- adrenoceptor ligand. MD-354, inactive by itself, potentiates the antinociceptive effects of an inactive dose of clonidine in the mouse tail- flick assay. An attempt to determine the underlying mechanism of this potentiating effect was the purpose of the present investigation. The studies focused on an examination of: i) MD-354 in the mouse hot-plate assay, ii) a more lipophilic analog of MD-354 in the tail-flick assay, iii) various analogs of MD-354 with different binding profiles in both mouse tail-flick and hot-plate assays. The present investigation suggests that both 5-HT3 and α2B- adrenoceptors are playing a role in the potentiation of clonidine analgesia by arylguanidines such as MD-354. Arylguanidines might represent a unique class of analgesia-enhancing agents with a dual (5-HT3/α2- adrenoceptor) mechanism of action.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Medicinal Chemistry

Year dc:date.available

2005

Author dc:creator

• Young, Shawquia Elithia

• ligands
• antinociception
• side effects
• receptor
• behavior
• Chemicals and Drugs
• Medicine and Health Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/1166

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-2165