DOI
https://doi.org/10.25772/82RW-BZ86
Defense Date
2005
Document Type
Thesis
Degree Name
Master of Science
Department
Medicinal Chemistry
Abstract
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.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
June 2008