Darroch S A, Taylor W C, Choo L K, Mitchelson F
School of Pharmacology, Victorian College of Pharmacy, Parkville, Victoria, Australia.
Eur J Pharmacol. 1990 Jun 21;182(1):131-6. doi: 10.1016/0014-2999(90)90501-v.
Himbacine, himbeline, N-methylhimandravine and himandravine together with their dihydro-derivatives were evaluated as antagonists of muscarinic receptors in guinea-pig ileal longitudinal muscle and electrically stimulated left atrium. Himbacine was the most potent compound and the 15-fold selectivity exhibited for the M2 muscarinic receptor was greater than that found with any of the other compounds examined. Reduction of the double bond linking the decalin ring system and the piperidine ring almost abolished selectivity in dihydrohimbacine. Removal of the N-methyl group in himbacine to form himbeline was associated with reduced selectivity. However the corresponding change in converting N-methylhimandravine to himandravine was not associated with any change in selectivity suggesting that orientation of the 2-methyl group in the piperidine ring may be important for selectivity.
对imbacine、himbeline、N-甲基himandravine和himandravine及其二氢衍生物进行了评估，以确定它们作为豚鼠回肠纵肌和电刺激左心房中毒蕈碱受体拮抗剂的活性。Himbacine是活性最强的化合物，对M2毒蕈碱受体表现出的15倍选择性高于所检测的任何其他化合物。连接十氢化萘环系统和哌啶环的双键还原几乎消除了二氢himbacine的选择性。Himbacine中N-甲基的去除形成himbeline与选择性降低有关。然而，将N-甲基himandravine转化为himandravine的相应变化与选择性的任何变化无关，这表明哌啶环中2-甲基的取向可能对选择性很重要。
