Characterization of ethyl (3-quinuclidinyl) acetate (EQA) as a ligand for acetylcholine receptors.
Recent studies suggest that neuronal nicotinic acetylcholine receptors (nAChRs) may play a role in several CNS disorders and that subtype selective nicotinic ligands may be useful in the treatment of these disorders. Ethyl (3-quinuclidinyl)acetate (EQA) is a bulky, reverse-ester analog of ACh, that produces signs of cholinergic stimulation that may be nicotinic in origin The objective of the present study was to further evaluate EQA as a potential cholinergic ligand. Behavioral studies, smooth muscle assays, and radioligand binding assays were performed on this novel ligand. The effects of EQA on blood pressure and acetylcholinesterase activity were also evaluated. The results of the study suggest that EQA is an agonist at peripheral nicotinic acetylcholine receptors and may have antagonist properties at central nicotinic receptors.
Canney
D J
DJ
Department of Pharmaceutical Sciences, Temple University, School of Pharmacy, Philadelphia, PA 19140, USA. canney@astro.temple.edu
Zhang
M
M
Doukas
P H
PH
Massakowski
C
C
Aronstam
R
R
Gattu
M
M
Buccafusco
J
J
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005069:Evaluation Studies as Topic; D008024:Ligands; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011812:Quinuclidines / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*
D008024:Ligands; D018733:Nicotinic Antagonists; D011812:Quinuclidines; D011978:Receptors, Nicotinic; C116170:ethyl(3-quinuclidinyl)acetate; D008464:Mecamylamine; D000110:Acetylcholinesterase; D000109:Acetylcholine