Antinociceptive effects of (+)-matrine in mice.
The antinociceptive potency of matridin-15-one ((+)-matrine) was examined using the acetic acid-induced abdominal contraction test and the tail-flick test in mice. (+)-Matrine, at doses of 1 to 10 mg/kg, s.c., produced a marked and dose-dependent inhibition of the number of acetic acid-induced abdominal contractions in mice. The antinociceptive effect of (+)-matrine in the acetic acid-induced abdominal contraction test in mice was identical to that of pentazocine. Indeed, there was no significant difference in the ED50 (mg/kg with 95% confidence limits) values for the inhibition of acetic acid-induced abdominal contractions between (+)-matrine (4.7 (4.1-5.3)) and pentazocine (3.3 (2.2-5.0)). Furthermore, in the tail-flick assay, (+)-matrine at doses of 10 and 30 mg/kg, s.c., again produced a dose-dependent antinociceptive effect. When nor-binaltorphimine (20 mg/kg, s.c.), a selective kappa-opioid receptor antagonist, was administered 3 h before treatment with (+)-matrine, the antinociceptive effect of (+)-matrine was markedly antagonized. Furthermore, the antinociceptive effect of (+)-matrine was partially antagonized by pretreatment with beta-funaltrexamine, a selective mu-opioid receptor antagonist. Naltrindole, a selective delta-opioid receptor antagonist, had no effect on the antinociceptive effect of (+)-matrine. In conclusion, (+)-matrine produced an antinociceptive effect mainly through the activation of kappa-opioid receptors and partially through mu-opioid receptors.
Kamei
J
J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan. kamei@hoshi.ac.jp
Xiao
P
P
Ohsawa
M
M
Kubo
H
H
Higashiyama
K
K
Takahashi
H
H
Li
J
J
Nagase
H
H
Ohmiya
S
S
D000005:Abdomen; D000470:Alkaloids / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009119:Muscle Contraction / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement; D011807:Quinolizines; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors; D013623:Tail; D000093842:Matrines
D000470:Alkaloids; D000700:Analgesics; D009292:Narcotic Antagonists; D011807:Quinolizines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; C055382:naltrindole; D000093842:Matrines