The current agonists and positive allosteric modulators of α 7 nAChR for CNS indications in clinical trials

Acta Pharm Sin B. 2017 Nov;7(6):611-622. doi: 10.1016/j.apsb.2017.09.001. Epub 2017 Oct 16.

Abstract

The alpha-7 nicotinic acetylcholine receptor (α7 nAChR), consisting of homomeric α7 subunits, is a ligand-gated Ca2+-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia. Currently, a number of α7 nAChR modulators have been reported and several of them have advanced into clinical trials. In this brief review, we outline recent progress made in understanding the role of the α7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of α7 nAChR modulators used in clinical trials.

Keywords: 5-CSRTT, five-choice serial reaction time task; 5-HT, serotonin; ACh, acetylcholine; AD, Alzheimer's disease; ADHD, attention deficit hyperactivity disorder; Acetylcholine; Alpha7; Alzheimer's disease; Aβ, amyloid-β peptide; CNS, central nervous system; DMTS, delayed matching-to-sample; ECD, extracellular domain; GABA, γ-aminobutyric acid; Ion channel; MLA, methyllycaconitine; NOR, novel object recognition; PAMs, positive allosteric modulators; PCP, neonatal phencyclidine; PD, Parkinson's disease; PPI, prepulse inhibition; Positive allosteric modulators; SAR, structure–activity relationship; Schizophrenia; TMD, transmembrane domains; nAChR; nAChR, nicotinic acetylcholine receptor; α-Btx, α-bungarotoxin.

Publication types

  • Review