Trzeciakowski J, Chiou C Y
J Pharm Sci. 1978 Apr;67(4):531-5. doi: 10.1002/jps.2600670423.
In attempts to find a drug more active than pilocarpine, the tertiary nitrogen derivative of carbachol, N-demethylated carbachol, was synthetized and tested on several autonomic nervous system preparations. N-Demethylated carbachol was active at muscarinic and nicotinic sites in vivo and in vitro. In superfusion studies, N-demethylated carbachol contracted the smooth muscle of the guinea pig ileum as well as skeletal muscles of frog recus abdominis and chick biventer cervicis. N-Demethylated carbachol decreased blood pressure in the rat, with an ED50 ("/- SEM) of 4.82 +/- 0.78 mg/kg. After close arterial injection to the cat superior cervical ganglion, N-demethylated carbachol elicited contractions of the nictitating membrane (ED50 of 1.68 +/- 0.24 mg/kg) that were not significantly affected by atropine. N-D-methylated carbachol stimulated salivation in dog Wharton duct preparations with an ED50 of 2.55 +/- 0.81 mg/kg. In contrast, pilocarpine had no effects on skeletal muscles in vitro, produced ganglionic effects blocked by atropine, had a prominent effect on salivation, and tended to elevate blood pressure.
为了找到一种比毛果芸香碱活性更强的药物，人们合成了卡巴胆碱的叔氮衍生物N-去甲基卡巴胆碱，并在多种自主神经系统制剂上进行了测试。N-去甲基卡巴胆碱在体内和体外的毒蕈碱和烟碱位点均有活性。在灌注研究中，N-去甲基卡巴胆碱使豚鼠回肠的平滑肌以及青蛙腹直肌和鸡颈二腹肌的骨骼肌收缩。N-去甲基卡巴胆碱使大鼠血压降低，半数有效剂量（ED50，±标准误）为4.82±0.78mg/kg。向猫颈上神经节进行动脉近距离注射后，N-去甲基卡巴胆碱引起瞬膜收缩（ED50为1.68±0.24mg/kg），且不受阿托品的显著影响。N-去甲基卡巴胆碱刺激犬颌下腺导管制剂分泌唾液，ED50为2.55±0.81mg/kg。相比之下，毛果芸香碱对体外骨骼肌无作用，产生的神经节效应可被阿托品阻断，对唾液分泌有显著作用，且有升高血压的倾向。
