Tetrahydroaminoacridinc discriminated slightly in its potency to displace [3H]N-methylscopolamine ([3H]NMS) binding from different muscarinic receptor subtypes (M2 > M1 > M3) and to allosterically decelerate ligand binding (M2 ≥ M1 > M3). T steep displacement curves suggest that marked changes in receptor occupancy may occur within a relatively narrow dose range. Thus, individual inter-patient variability and inconsistent results in clinical studies may be related to blockade of muscarinic receptors, which would oppose the beneficial effects resulting from acetylcholinesterase inhibition.
Bibliographical noteFunding Information:
This studyw as supportedi n part by Grants NS2S743a nd AG-07118f rom the National Institutes of Health and by Contract DAAL-03-K-88-0078 from the U.S. Army Research Office. J. S. K. was a recipient of an Emerson FelIowship from the Universityo f Marylandd uringthe courseo f this work. E. E. E. is a recipiento f a ResearchC areer Development Award from the National fnstitutes of Health (AC-00344). The authors would like to thankM ike Gentry for his excellent technical assistance.
Copyright 2014 Elsevier B.V., All rights reserved.
- Allosteric antagonists
- Muscarinic receptor subtypes
- Muscarinic receptors