title: Ginsenoside Rf potentiates U-50,488H-induced analgesia and inhibits tolerance to its analgesia in mice.
abstract: In the present study, the effect of ginsenoside Rf (Rf), a trace component of Panax ginseng on U-50,488H (U50), a selective kappa opioid-induced analgesia and its tolerance to analgesia was studied using the mice tail-flick test. In addition, the possible mechanism by which Rf may affect U50-induced analgesia was investigated. Intraperitoneal administration of U50 (40 mg/kg) produced analgesia. Rf (10(-14)-10(-10) mg/kg) on co treatment dose-dependently potentiated the U50 (40 mg/kg)-induced analgesia. Rf (10(-12)-10(-2) mg/ml) did not alter the binding of [3H] naloxone, a opioid ligand and [3H]PN200-110, a dihydropyridine ligand to mice whole brain membrane. Twice daily administration of U50 (40 mg/kg) for six days induced tolerance to its analgesia. Chronic treatment (day 4-day 6) of Rf (10(-14)-10(-10) mg/kg) to U50-tolerant mice, dose-dependently inhibited the tolerance. The inhibition of tolerance to U50-induced analgesia by Rf was not altered by flumazenil (0.1 mg/kg), a benzodiazepine receptor antagonist and picrotoxin (1 mg/kg), a GABA(A)-gated chloride channel blocker on chronic treatment. In conclusion, these findings for the first time demonstrated that ginsenoside Rf potentiates U50-induced analgesia, inhibits tolerance to its analgesia, and suggests that Rf affects U50-induced analgesia via non-opioid, non-dihydropyridine-sensitive Ca(+2) and non-benzodiazepine-GABA(A)ergic mechanisms in mice.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Phase-X, S. A. S., Nagar-160 062 (Pb), India.
authors.forename: Kumar V S
authors.initials: KV
authors.lastname: Nemmani
authors.forename: P
authors.initials: P
authors.lastname: Ramarao
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000008:administration & dosage / Q000494:pharmacology*; D000698:Analgesia; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004361:Drug Tolerance; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000494:pharmacology*; D036145:Ginsenosides / Q000378:metabolism / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D017275:Isradipine / Q000378:metabolism; D008297:Male; D051379:Mice; D009270:Naloxone / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D013623:Tail / Q000187:drug effects
chemical_list: D018712:Analgesics, Non-Narcotic; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D009270:Naloxone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C055328:ginsenoside Rf; D017275:Isradipine