Antinociceptive effects of N-acyloctahydropyrido[3,2,1-ij][1,6]naphthyridine in mice: structure-activity relation study of matrine-type alkaloids part II.
N-Acyloctahydropyrido[3,2,1-ij][1,6]naphthyridines were synthesized as derivatives of matrine-type alkaloids, and the structure-activity relations were examined by the acetic acid-induced abdominal contraction test. The antinociceptive potencies of N-acyloctahydropyrido[3,2,1-ij][1,6]naphthyridines were significantly lower than those of (+)-matrine. The antinociceptive effects of N-benzyloctahydropyrido[3,2,1-ij][1,6]naphthyridines are approximately 5.6 to 6.5 times less than those of N-benzoyloctahydropyrido[3,2,1-ij][1,6]naphthyridine. These findings suggest that the amide group of matrine-type alkaloids is an essential functional group that influences antinociceptive potency. The antinociceptive effect of 4c was markedly antagonized by pretreatment with Naloxone, and that of 3c partially so.
Kobashi
Seiichi
S
Faculty of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, Japan.
Takizawa
Masayuki
M
Kubo
Hajime
H
Yamauchi
Takayasu
T
Higashiyama
Kimio
K
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006571:Heterocyclic Compounds; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects*; D011807:Quinolizines; D012020:Reflex, Abdominal / Q000187:drug effects; D013329:Structure-Activity Relationship; D000093842:Matrines
D000470:Alkaloids; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006571:Heterocyclic Compounds; D009292:Narcotic Antagonists; D011807:Quinolizines; D009270:Naloxone; D000093842:Matrines