The effects of a new cholinolytic--8018--and its optical isomers on the central muscarinic and nicotinic receptors.
3-(2'-phenyl-2'-cyclopentyl-2'-hydroxyl-ethoxy)quinuclidine (8018), a new cholinolytic, is a racemic tertiary amine with two chiral carbonic atoms. It has 4 optical isomers whose absolute configurations are RR', SR', RS' and SS'. These compounds showed potent pharmacological activity, blocking both central muscarinic and nicotinic receptors. Central muscarinic receptors, rather than nicotinic receptors, have a stereoselective specificity to these compounds. The R configuration of both substituted alkoxyl and alkalinic alcohol parts is more suitable to the stereostructure of the binding site of muscarinic receptors than the S configuration. These compounds can prevent soman-induced electroencephalographic seizures in rats by both their central M- and N-cholinolytic actions.
Niu
W Z
WZ
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
Zhao
D L
DL
Liu
C G
CG
D000818:Animals; D001115:Arecoline / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D003517:Cyclopentanes / Q000378:metabolism / Q000494:pharmacology*; D004569:Electroencephalography; D005260:Female; D008297:Male; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology*; D011812:Quinuclidines / Q000378:metabolism / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D012999:Soman / Q000494:pharmacology; D013237:Stereoisomerism; D014202:Tremor / Q000139:chemically induced / Q000503:physiopathology
D003517:Cyclopentanes; D010276:Parasympatholytics; D011812:Quinuclidines; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; C066419:3-(2'-phenyl-2'-cyclopentyl-2'-hydroxyethoxy)quinuclidine; D001115:Arecoline; D011813:Quinuclidinyl Benzilate; D009538:Nicotine; D012999:Soman