Antinociceptive effects of 1-acyl-4-dialkylaminopiperidine and 1-alkyl-4-dialkylaminopiperidine in mice: structure-activity relation study of matrine-type alkaloids.
We previously reported that (+)-matrine and (+)-allomatrine have antinociceptive properties mediated mainly through the activation of kappa-opioid receptors. 1-Acyl-4-dialkylaminopiperidines were synthesized as the simplest derivatives of matrine, and the structure-activity relations were examined by the acetic acid-induced abdominal contraction test. The antinociceptive potencies of 1-alkyl-4-dialkylaminopiperidines were significantly lower than those of the corresponding 1-acyl-4-dialkylaminopiperidines. These findings suggest that the amide group of (+)-matrine is an essential functional group that influences antinociceptive potency.
Kobashi
Seiichi
S
Faculty of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
Kubo
Hajime
H
Yamauchi
Takayasu
T
Higashiyama
Kimio
K
D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010880:Piperidines / Q000737:chemistry* / Q000494:pharmacology*; D011807:Quinolizines; D013329:Structure-Activity Relationship; D000093842:Matrines
D000470:Alkaloids; D000700:Analgesics; D010880:Piperidines; D011807:Quinolizines; D000093842:Matrines