Abood L G, Shahid Salles K, Maiti A
Department of Pharmacology, University of Rochester, School of Medicine and Dentistry, NY 14642.
Pharmacol Biochem Behav. 1988 Jun;30(2):403-8. doi: 10.1016/0091-3057(88)90475-3.
A number of aromatic, cycloalkyl, and heterocyclic carbamic acid esters, thiocarbamic acid esters, and carboxylic acid esters of di- and trial-kylaminoalkyl and heterocyclic amino alcohols have been synthesized and tested for their pharmacologic and receptor binding characteristics at the nicotine receptor. Receptor binding was measured in rat brain membranes using (-)-3H-nicotine or 3H-methylcarbamylcholine as radioligands. The compounds were tested for their ability to produce seizures and prostration and to antagonize the nicotine-induced prostration and seizures as well as the hypertensive action of nicotine in rats. Among the potent agonists were the N-methylcarbamyl and N-methylthiocarbamyl esters of choline (trimethylaminoethanol), with the tertiary amino derivatives between considerably less potent than the quaternary. Potent antagonists included trimethylaminoethyl benzoate, 3-quinuclidinyl benzoate, and trimethylaminoethyl esters of phenyl and phenylthiocarbamic acids. One of the most potent antagonists to nicotine was alpha-lobeline.
已经合成了多种二烷基和三烷基氨基烷基醇以及杂环氨基醇的芳香族、环烷基和杂环氨基甲酸酯、硫代氨基甲酸酯和羧酸酯，并测试了它们在尼古丁受体上的药理和受体结合特性。使用（-）-3H-尼古丁或3H-甲基氨甲酰胆碱作为放射性配体，在大鼠脑膜中测量受体结合。测试了这些化合物诱发癫痫和虚脱的能力，以及拮抗尼古丁诱发的虚脱和癫痫以及尼古丁对大鼠的高血压作用的能力。强效激动剂包括胆碱（三甲基氨基乙醇）的N-甲基氨甲酰酯和N-甲基硫代氨甲酰酯，叔氨基衍生物的效力明显低于季铵衍生物。强效拮抗剂包括苯甲酸三甲基氨基乙酯、苯甲酸3-喹啉基酯以及苯基和苯硫代氨基甲酸的三甲基氨基乙酯。对尼古丁最有效的拮抗剂之一是α-洛贝林。
