Acta Pharmaceutica Sinica B 2017;7(6):611-622

doi:10.1016/j.apsb.2017.09.001

The current agonists and positive allosteric modulators of7 nAChR for CNS indications in clinical trials.

Taoyi YANG 1 ; Ting XIAO 1 ; Qi SUN 2 ; Kewei WANG 1

Affiliations

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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

Country

China

Language

English

Abstract

The alpha-7 nicotinic acetylcholine receptor (7 nAChR), consisting of homomeric7 subunits, is a ligand-gated Ca-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of7 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 of7 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 the7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of7 nAChR modulators used in clinical trials.