Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia

  title={Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia},
  author={Laura F. Martin and William R. Kem and Robert Freedman},
Rationale and objectiveAuditory sensory gating, a biological measurement of the ability to suppress the evoked response to the second of two auditory stimuli, is diminished in people with schizophrenia. Deficits in sensory gating are associated with attentional impairment, and may contribute to cognitive symptoms and perceptual disturbances. This inhibitory process, which involves the alpha7 nicotinic receptor mediated release of gamma-aminobutyric acid (GABA) by hippocampal interneurons… 
Schizophrenia and the alpha7 nicotinic acetylcholine receptor.
Targeting of α7 Nicotinic Acetylcholine Receptors in the Treatment of Schizophrenia and the Use of Auditory Sensory Gating as a Translational Biomarker
  • K. Hashimoto
  • Psychology, Medicine
    Current pharmaceutical design
  • 2015
Recent findings on α7 nAChR agonists such as DMXB-A, RG3487, TC-5619, tropisetron, EVP-6124 (encenicline), ABT-126, AQW051 and α7nA ChR PAMs are discussed, and their potential as therapeutic drugs for neuropsychiatric diseases, such as schizophrenia is discussed.
Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function.
α7 Nicotinic Receptor Agonists: Potential Therapeutic Drugs for Treatment of Cognitive Impairments in Schizophrenia and Alzheimer’s Disease
Based on the recent research into the role of α7 nAChRs in the pathophysiology of these diseases and into the potential use of novel α7nAChR agonists as therapeutic drugs, selective α7NAs can be considered potential therapeutic drugs for cognitive impairments in both schizophrenia and AD.
The quest for the treatment of cognitive impairment: α7 nicotinic and α5 GABAA receptor modulators
This article reviews the patents on modulators of α7 nicotinic acetylcholine and GABAA receptors disclosed during the period 2000 – 2006 and seems at present the most important GabAA receptor subtype involved in cognitive processes.
Targeting α7 Nicotinic Acetylcholine Receptors in the Treatment of Schizophrenia
Recent development of selective agonists and positive allosteric modulators of alpha7 nAChRs are discussed and the association between CHRNA7 gene and impaired P50 auditory gating has provided an attractive endophenotype.
Nicotinic receptors and attention.
  • Britta Hahn
  • Biology, Psychology
    Current topics in behavioral neurosciences
  • 2015
Neuroimaging studies suggest that nAChR agonists act on a variety of brain systems by enhancing activation, reducing activation, and enhancing deactivation by attention tasks, which supports the notion that effects on different attentional functions may be mediated by distinct central mechanisms, consistent with the fact thatnAChRs interact with a multitude of brain sites and neurotransmitter systems.


Schizophrenia, sensory gating, and nicotinic receptors.
The receptor's possible role in cell growth and differentiation should be considered in connection with developmental deficits and other cellular abnormalities in schizophrenia, and heavy smoking in many schizophrenia patients is consistent with the high concentration of nicotine necessary to activate the receptor and with the receptor's extremely rapid desensitization.
Schizophrenia and Nicotinic Receptors
The clinical phenomenology of inhibitory gating deficits in people with schizophrenia, the neurobiology of such gating mechanisms, and the evidence that some individuals with the disorder may have a heritable deficit in the nicotinic cholinergic receptors involved in this neurobiological function are reviewed.
Neuronal Nicotinic Receptors in Dementia with Lewy Bodies and Schizophrenia
It is concluded that widespread abnormalities of thalamic nicotine are not implicated in schizophrenia or DLB, but that reticular αBGT binding may be involved to a lesser and greater extent in the pathophysiology or psychopathology of both disorders.
Development of nicotinic drug therapy for cognitive disorders.
Selective α7-nicotinic agonists normalize inhibition of auditory response in DBA mice
The results indicated that the anabaseine compounds increase sensory inhibition through α7 nicotinic receptors, and that their ability to act repeatedly on these receptors may be less affected by desensitization.
Abnormal Regulation of High Affinity Nicotinic Receptors in Subjects with Schizophrenia