Oxymatrine inhibits development of morphine-induced tolerance associated with decreased expression of P-glycoprotein in rats.
The effect of oxymatrine on the development of tolerance to the antinociceptive effects of morphine was investigated in rats. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily administration of oxymatrine premorphine (10/20/30 mg/kg). High doses of oxymatrine inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg of the NMDA receptor antagonist memantine) while also increasing the antinociceptive effects. A high dose of oxymatrine (30 mg/kg) also significantly inhibited the dramatic increase in expression of morphine-induced P-glycoprotein (P-gp), an ATP-dependent efflux pump acting at the blood-brain barrier, by Western blot analysis. Furthermore, these studies suggest that P-gp modulates the development of morphine tolerance while not affecting the magnitude of the analgesic effect of morphine. These results imply that oxymatrine prevention of the development of tolerance of morphine may be related to a considerable inhibition of P-gp expression. In contrast, the authors' data suggest that the mechanism of oxymatrine enhancement of morphine's analgesic effects is not associated with increase in the level of expression of P-gp. However, they believe that their findings can be used by researchers to develop therapies that will allow patients to take morphine without becoming tolerant of its benefits.
Li
Yanwei
Y
Cancer Center of Integrated Traditional and Western Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. liyanwei127@hotmail.com
Yue
Hui
H
Xing
Yanmin
Y
Sun
Haiyan
H
Pan
Zhanyu
Z
Xie
Guangru
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000235:genetics; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy; D011807:Quinolizines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000093842:Matrines
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D000701:Analgesics, Opioid; D009020:Morphine; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines