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Many different<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>subtypes exist with each their functional characteristics, expression pattern and pharmacological profile. The focus of the present MiniReview is on the heteromeric \u03b14\u03b22<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>, as activity at this subtype contributes to cognitive functioning through interactions with multiple neurotransmitter systems and is implicated in various<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>disorders, for example schizophrenia and Alzheimer's disease. Additionally, the \u03b14\u03b22<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>provides an extra layer of molecular complexity by existing in two different stoichiometries determined by the subunit composition. Such findings have founded the rationale that pharmacological modulation of the \u03b14\u03b22<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>may be used as a treatment approach in various<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>disorders. As subtype\u2010selective agonists and other cholinergic ligands have only shown limited therapeutic success, the focus of recent drug development endeavours has largely shifted to positive allosteric modulators (<jats:styled-content style=\"fixed-case\">PAM<\/jats:styled-content>s). By potentiating the action of an agonist through binding to an allosteric site, a<jats:styled-content style=\"fixed-case\">PAM<\/jats:styled-content>can enhance cholinergic neurotransmission, thus compensating for compromised neuronal communication in a pathophysiological setting. The pharmacological advantages of<jats:styled-content style=\"fixed-case\">PAM<\/jats:styled-content>s compared to other types of ligands include minimal interference with spatial and temporal aspects of neurotransmission as well as higher subtype selectivity, hypothetically resulting in high clinical efficacy with minimal adverse effects. In this MiniReview, we describe the currently identified compounds, which potentiate the effects of agonists at the \u03b14\u03b22<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>. The potential clinical advantages and concerns of<jats:styled-content style=\"fixed-case\">PAM<\/jats:styled-content>s are discussed in the light of the role of \u03b14\u03b22<jats:styled-content style=\"fixed-case\">nAChR<\/jats:styled-content>s as key regulators of fast synaptic transmission.<\/jats:p>","DOI":"10.1111\/bcpt.12361","type":"journal-article","created":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T17:40:19Z","timestamp":1417455619000},"page":"187-200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Targeting \u03b14\u03b22 Nicotinic Acetylcholine Receptors in Central Nervous System Disorders: Perspectives on Positive Allosteric Modulation as a Therapeutic Approach"],"prefix":"10.1111","volume":"116","author":[{"given":"Morten","family":"Grupe","sequence":"first","affiliation":[{"name":"Synaptic Transmission H. 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