Pharmacological activity and receptor-binding characteristics of 2 beta-(2'-phenyl-2'-cyclopentyl-2'-hydroxy-ethoxy)tropane and its optical isomers.
This study describes the receptor-binding characteristics, antimuscarinic and antinicotinic activities of 2 beta-(2'-phenyl-2'-cyclopentyl-2'-hydroxy-ethoxy)tropane (beta-PCT) and its four optical isomers. Both arecoline-induced tremor and nicotine-induced convulsion in mice were antagonized by beta-PCT and its optical isomers. These compounds were less potent than atropine in their antimuscarinic potencies, but more potent than atropine in their antinicotinic activities. The isomer with the 1S-2 beta-2'R configuration was about one order of magnitude more potent than the isomer with the 1R-2 beta-2'S configuration in their antimuscarinic activity, but the antinicotinic potencies of these compounds did not differ significantly. The order of potencies of beta-PCT and its optical isomers to displace the specific binding of [3H]quinuclidinyl benzilate to muscarinic receptors was similar to that of their antimuscarinic potencies. The binding of [3H]nicotine to central nicotinic receptors was not inhibited by these compounds. The findings indicate that beta-PCT and its optical isomers are useful affinity ligands to examine the biochemical and functional characteristics of brain cholinergic receptors.
Gao
Z G
ZG
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
Cui
W Y
WY
Wang
L
L
Liu
C G
CG
D000818:Animals; D001115:Arecoline / Q000008:administration & dosage / Q000633:toxicity; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007553:Isotope Labeling; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000633:toxicity; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D013237:Stereoisomerism; D014202:Tremor / Q000139:chemically induced / Q000188:drug therapy; D014316:Tritium; D014326:Tropanes / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D014326:Tropanes; D014316:Tritium; C094207:2-(2'-cyclopentyl-2'-phenyl-2'-hydroxyethoxy)tropane; D001115:Arecoline; D011813:Quinuclidinyl Benzilate; D009538:Nicotine; D001285:Atropine