Preparation and affinity profile of novel nicotinic ligands.
Novel nicotinic ligands, characterized by the presence of an amino substituted cyclopropane ring connected to a pyridine nucleus, are described. Pharmacological investigation revealed that these compounds exhibit highest affinity for the rat alpha4beta2 subtype of the nicotinic receptor with no affinity for the muscarinic receptor. No appreciable affinity for the muscular or for the ganglionic nicotinic receptor was observed at concentrations up to 10 microM. The increase in cortical ACh release as well as a positive effect on memory in a social recognition test in rat are exemplified.
Charton
Yves
Y
SERVIER, Chemistry Research Division A, 11 rue des Moulineaux, 92150 Suresnes, France.
Guillonneau
Claude
C
Lockhart
Brian
B
Lestage
Pierre
P
Goldstein
Solo
S
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D003521:Cyclopropanes / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008568:Memory / Q000187:drug effects; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*
D003521:Cyclopropanes; D018722:Nicotinic Agonists; D011725:Pyridines; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C030797:cyclopropane; D000109:Acetylcholine; C023666:pyridine