Abstract
A series of 3'-(substituted phenyl)deschloroepibatidine analogs (5a-j) were synthesized. The alpha4beta2( *) and alpha7 nicotinic acetylcholine receptor (nAChR) binding properties and functional activity in the tail-flick, hot-plate, locomotor, and body temperature tests in mice of 5a-j were compared to those of the nAChR agonist, nicotine (1), epibatidine (4), and deschloroepibatidine (13), the partial agonist, varenicline (3), and the antagonist 2'-fluoro-3'-(substituted phenyl)deschloroepibatidine analogs (7a-j). Unlike epibatidine and deschloroepibatidine, which are potent agonists in the tail-flick test, 5a-k show no or very low antinociceptive activity in the tail-flick or hot-plate test. However, they are potent antagonists in nicotine-induced antinociception in the tail-flick test, but weaker than the corresponding 2'-fluoro-3'-(substituted phenyl)deschloroepibatidines.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Analgesics / chemical synthesis*
-
Analgesics / metabolism
-
Analgesics / pharmacology
-
Animals
-
Body Temperature
-
Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
-
Bridged Bicyclo Compounds, Heterocyclic / metabolism
-
Bridged Bicyclo Compounds, Heterocyclic / pharmacology
-
Cerebral Cortex / metabolism
-
Disease Models, Animal
-
Dose-Response Relationship, Drug
-
Mice
-
Molecular Structure
-
Nicotinic Antagonists / chemical synthesis*
-
Nicotinic Antagonists / metabolism
-
Nicotinic Antagonists / pharmacology
-
Pain / prevention & control
-
Protein Binding
-
Pyridines / chemical synthesis*
-
Pyridines / metabolism
-
Pyridines / pharmacology
-
Radioligand Assay
-
Receptors, Nicotinic / metabolism*
-
Structure-Activity Relationship
Substances
-
Analgesics
-
Bridged Bicyclo Compounds, Heterocyclic
-
Nicotinic Antagonists
-
Pyridines
-
Receptors, Nicotinic
-
epibatidine