Characterization of AN317, a novel selective agonist of α6β2-containing nicotinic acetylcholine receptors.

Characterization of AN317, a novel selective agonist of α6β2-containing nicotinic acetylcholine receptors. Biochem Pharmacol. 2019 Dec 27;:113786 Authors: Sandager-Nielsen K, Ahring PK, Klein J, Hout MV, Thaneshwaran S, Santos ABD, Jacobsen TA, Amrutkar DV, Peters D, Jensen AA, Kohlmeier KA, Christophersen P, Dyhring T Abstract Neuronal nicotinic acetylcholine receptors (nAChRs) are crucial mediators of central presynaptic, postsynaptic, and extrasynaptic signaling, and they are implicated in a range of CNS disorders. The numerous nAChR subtypes are differentially expressed and mediate distinct functions throughout the CNS, and thus there is considerable interest in developing subtype-selective nAChR modulators, both for use as pharmacological tools and as putative therapeutics. α6β2-containing (α6β2*) nAChRs are highly expressed in and regulate the activity of midbrain dopaminergic neurons, which makes them attractive drug targets in several psychiatric and neurological diseases, including nicotine addiction and Parkinson's disease. This paper presents the preclinical characterization of AN317, a novel α6β2* agonist exhibiting functional selectivity toward other nAChRs, including α4β2, α3β4 and α7 receptors. AN317 induced [3H]dopamine release from rat striatal synaptosomes and augmented dopaminergic neuron activity in substantia nigra pars compacta brain slices in Ca2+ imaging and electrophysiological assays. In line wi...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research