Structure-activity studies of carbamate and other esters: agonists and antagonists to nicotine.
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.
Abood
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Department of Pharmacology, University of Rochester, School of Medicine and Dentistry, NY 14642.
Shahid Salles
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K
Maiti
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D000818:Animals; D002217:Carbachol / Q000031:analogs & derivatives*; D002219:Carbamates / Q000494:pharmacology*; D002264:Carboxylic Acids / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D004952:Esters / Q000494:pharmacology*; D008024:Ligands; D009538:Nicotine / Q000037:antagonists & inhibitors*; D011619:Psychotropic Drugs / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013329:Structure-Activity Relationship
D002219:Carbamates; D002264:Carboxylic Acids; D004952:Esters; D008024:Ligands; D011619:Psychotropic Drugs; D011978:Receptors, Nicotinic; C053765:N-methylcarbamylcholine; D009538:Nicotine; D002217:Carbachol; D002794:Choline