title: Opioids and efflux transporters. Part 2: P-glycoprotein substrate activity of 3- and 6-substituted morphine analogs.
abstract: Continuing our studies investigating opioids with reduced P-glycoprotein (P-gp) substrate activity, a series of known 3- and 6-hydroxy, -methoxy, and -desoxymorphine analogs was synthesized and analyzed for P-gp substrate activity and opioid binding affinity. 6-Desoxymorphine ( 7) showed high affinity for opioid receptors and did not induce P-gp-mediated ATP hydrolysis. Additionally, 7 demonstrated morphine-like antinociceptive potency in mice, indicating this compound as an ideal lead to further evaluate the role of P-gp in opioid analgesic tolerance development.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, MD 21201, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Cunningham
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mercer
authors.forename: Hazem E
authors.initials: HE
authors.lastname: Hassan
authors.forename: John R
authors.initials: JR
authors.lastname: Traynor
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Eddington
authors.forename: Andrew
authors.initials: A
authors.lastname: Coop
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000187:drug effects*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D051379:Mice; D008968:Molecular Conformation; D009022:Morphine Derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C529452:6-desoxymorphine; D018435:ATP Binding Cassette Transporter, Subfamily B; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D011957:Receptors, Opioid