Glycopeptides as Analgesics: Non-Toxic Alternatives to Morphine for Combat Casualty Care
Abstract
Background: Endogenous opiate peptides (enkephalins and endorphins) are more potent and specific than morphine and congeners. Specificity is determined by the "address segment" while binding is determined by the "message segment." Incorporation of carbohydrates into the address segment results in improved biodistribution and enhanced penetration of the blood-brain barrier (BBB). Thus, glycosylation of mu- or delta-selective peptides allows the resulting glycopeptides to be used as potent and safer alternatives to classical opiates such as morphine. Morphine and other mu- selective agonists are immunosuppressants, while the glycopeptide enkephalins are selective delta-agonists, which are known to be immunostimulants. Hypothesis: Enkephalin transport and penetration of the blood-brain barrier can be determined by reversible binding to membranes, which may be manipulated by altering the amphipathicity of the address segment directly by introduction of hydrophilic sugar moieties, and lipophilic side chains. Conclusion: Glycopeptide analogues of enkephalins are viable drug candidates. Obstacles regarding the synthesis and design of analgesics have been overcome. Further studies are required in order to understand the clinical implications of their use both in a hospital setting, as well as on the battlefield, and also in order to meet FDA requirements.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2005
- Accession Number
- ADA448229
Entities
People
- Robin Polt
Organizations
- University of Arizona