Novel allosteric effects of amiodarone at the muscarinic M5 receptor.

ABSTRACT: Allosteric sites on muscarinic receptors may present superior therapeutic targets for several central nervous system disorders, due to the potential of allosteric ligands to provide more selective modulation and to preserve the spatiotemporal patterning that is characteristic of synaptic transmission. We have found that the antiarrhythmic drug amiodarone interacts allosterically with M(1) and M(5) muscarinic receptors. At both M(1) and M(5), amiodarone was only able to partially inhibit the binding of the orthosteric antagonist [(3)H]N-methylscopolamine (NMS). In addition, amiodarone was able to alter the rate of dissociation of [(3)H]NMS from M(1) and M(5) receptors. These findings suggest that NMS and amiodarone are able to bind to the receptor simultaneously. The pharmacology of the eff

SUBMITTER: Stahl E 

PROVIDER: S-EPMC2912050 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature