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.
Arsequell
Gemma
G
Unit of Glycoconjugate Chemistry, Instituto de Química Avanzada de Cataluña (IQAC-CSIC), Barcelona, Jordi Girona 18-26, E08034-Barcelona, Spain.
Salvatella
Mariona
M
Valencia
Gregorio
G
Fernández-Mayoralas
Alfonso
A
Fontanella
Marco
M
Venturi
Chiara
C
Jiménez-Barbero
Jesús
J
Marrón
Ezequiel
E
Rodríguez
Raquel E
RE
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