Synthesis, conformation, and biological characterization of a sugar derivative of morphine that is a potent, long-lasting, and nontolerant antinociceptive.
A synthetic mannoside derivative, namely, 6-morphinyl-alpha-D-mannopyranoside, shows a naloxone-reversible antinociception that is 100-fold more potent and twice as long lasting compared to morphine when administered intraperitoneally to rats in paw pressure and tail flick tests. The compound does not produce tolerance and binds to rat mu opioid receptors with twice the affinity of morphine. NMR studies suggest that differences of activity between the derivative and its parent compound M6G might be related to their differing molecular dynamic behavior.
Unit of Glycoconjugate Chemistry, Instituto de Química Avanzada de Cataluña (IQAC-CSIC), Barcelona, Jordi Girona 18-26, E08034-Barcelona, Spain.
Gemma
G
Arsequell
Mariona
M
Salvatella
Gregorio
G
Valencia
Alfonso
A
Fernández-Mayoralas
Marco
M
Fontanella
Chiara
C
Venturi
Jesús
J
Jiménez-Barbero
Ezequiel
E
Marrón
Raquel E
RE
Rodríguez
D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004361:Drug Tolerance; D008297:Male; D008362:Mannosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D009020:Morphine / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D009022:Morphine Derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013997:Time Factors
C540942:6-morphinylmannopyranoside; D000700:Analgesics; D008362:Mannosides; D009022:Morphine Derivatives; D017450:Receptors, Opioid, mu; D009020:Morphine