Majonoside-R2, a major constituent of Vietnamese ginseng, attenuates opioid-induced antinociception.
The effects of majonoside-R2 on antinociceptive responses caused by the mu-opioid receptor agonist morphine and the selective kappa-opioid receptor agonist U-50, 488H were examined by the tail-pinch test in mice. Intraperitoneal (IP) or intracerebroventricular (ICV) injection of majonoside-R2 (3.1-6.2 mg/kg, IP or 5-10 micrograms/mouse, ICV) and diazepam (0.1-0.5 mg/kg, IP or 0.5-1.0 microgram/mouse, ICV), as well as an opioid receptor antagonist naloxone (2 mg/kg, IP or 5 micrograms/mouse, ICV), dose-dependently attenuated the antinociception caused by subcutaneously administered morphine and U-50,488H. Moreover, when co-administered ICV or intrathecally (IT) with morphine (4 micrograms/mouse) or U-50,488H (60 micrograms/mouse), majonoside-R2 (5-20 micrograms/mouse) also exhibited antagonism against the antinociceptive action of these opioid receptor agonists in the tail-pinch test. The inhibitory effects of majonoside-R2 (10 micrograms/mouse, ICV) and diazepam (1 microgram/mouse, ICV) were reversed by flumazenil (2.5 micrograms/mouse, ICV), a selective benzodiazepine receptor antagonist, and picrotoxin (0.25 microgram/mouse, ICV), a GABA-gated chloride channel blocker. These results suggest that majonoside-R2 attenuates the opioid-induced antinociception by acting at the spinal and supraspinal levels, and that the GABAA receptor complex at the supraspinal level is involved in the effect of ICV administered majonoside-R2.
Huong
N T
NT
Department of Pharmacology, Research Institute for Wakan-Yaku (Oriental Medicines), Toyama Medical and Pharmaceutical University, Japan.
Matsumoto
K
K
Yamasaki
K
K
Duc
N M
NM
Nham
N T
NT
Watanabe
H
H
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors*; D000818:Animals; D003975:Diazepam / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D036145:Ginsenosides; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000037:antagonists & inhibitors*; D010147:Pain Measurement; D005894:Panax / Q000737:chemistry*; D010946:Plants, Medicinal; D011759:Pyrrolidines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D014744:Vietnam
D000700:Analgesics; D000701:Analgesics, Opioid; D018756:GABA Antagonists; D036145:Ginsenosides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012503:Saponins; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C098043:majonoside R2; D003975:Diazepam