Effects of a new cholinolytic drug of tropanes and its optical isomers on central muscarinic and nicotinic receptors.
2 alpha-(2',2'-disubstituted-2'-hydroxy-ethoxy)tropane (2 alpha-DHET cholinolytic, is a racemic tertiary amine with two chiral carbonic atoms. It has four optical isomers whose absolute configurations are 1R-2 alpha-2'S, 1R-2 alpha-2'R 1S-2 alpha'R and 1S-2 alpha-2'S. These compounds showed both antimuscarinic and antinicotinic activity, blocking both muscarinic and nicotinic receptors. Central muscarinic receptors, rather than nicotinic receptors, have a stereoselective specificity to these compounds. The 2'R configurations are more suitable to the stereostructure of the binding site of muscarinic receptors than the 2'S configuration.
Gao
Z G
ZG
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, People's Republic of China.
Wang
L
L
Liu
C G
CG
Zhang
Q K
QK
D000818:Animals; D001835:Body Weight; D005260:Female; D008297:Male; D008968:Molecular Conformation; D018727:Muscarinic Antagonists / Q000378:metabolism; D016548:Prosencephalon / Q000737:chemistry / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D014326:Tropanes / Q000737:chemistry / Q000378:metabolism*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D014326:Tropanes; C094207:2-(2'-cyclopentyl-2'-phenyl-2'-hydroxyethoxy)tropane; D011813:Quinuclidinyl Benzilate