Nicotinic Receptor Agonists: Potential Therapeutic Drugs for Treatment of Cognitive Impairments in Schizophrenia and Alzheimer’s Disease. Open Med Chem J 4:37-56

Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
The Open Medicinal Chemistry Journal 05/2010; 4:37-56. DOI: 10.2174/1874104501004010037
Source: PubMed


Accumulating evidence suggests that α7 nicotinic receptors (α7 nAChRs), a subtype of nAChRs, play a role in the pathophysiology of neuropsychiatric diseases, including schizophrenia and Alzheimer's disease (AD). A number of psychopharmacological and genetic studies shown that α7 nAChRs play an important role in the deficits of P50 auditory evoked potential in patients with schizophrenia, and that (α nAChR agonists would be potential therapeutic drugs for cognitive impairments associated with P50 deficits in schizophrenia. Furthermore, some studies have demonstrated that α7 nAChRs might play a key role in the amyloid-β (Aβ)-mediated pathology of AD, and that α7 nAChR agonists would be potential therapeutic drugs for Aβ deposition in the brains of patients with AD. Interestingly, the altered expression of α7 nAChRs in the postmortem brain tissues from patients with schizophrenia and AD has been reported. Based on all these findings, selective α7 nAChR agonists can be considered potential therapeutic drugs for cognitive impairments in both schizophrenia and AD. In this article, we review the recent research into the role of α7 nAChRs in the pathophysiology of these diseases and into the potential use of novel α7 nAChR agonists as therapeutic drugs.

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    • "Several α7 nAChR-selective radioligands such as PNU- 282987 [8], [9],PHA-543613 [10],AR-R17779 [11],SSR180711[12]–[15] and A-582941 [16] have already been tested in animal and human studies. It is therefore likely that α7 nAChR agonists will be useful as therapeutic drugs for cognitive deficits in several neuropsychiatric diseases [17]. "
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    PLoS ONE 07/2013; 8(7):e70188. DOI:10.1371/journal.pone.0070188 · 3.23 Impact Factor
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    • "Growing evidence suggests that a deficit in cholinergic neurotransmission plays an important role in mediating cognitive deficits (Araki et al., 2002; Levin, 2002; Money et al., 2012). This evidence suggests that activation of the nicotinic receptors can be useful in treating some symptoms of schizophrenia particularly the cognitive deficits (Taly et al., 2009; Toyohara and Hashimoto, 2010). "
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    Frontiers in Pharmacology 10/2012; 3:173. DOI:10.3389/fphar.2012.00173 · 3.80 Impact Factor
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    • "The final evidence that the vagal anti-inflammatory pathway is indeed a breakthrough for the clinical management of immune-mediated inflammatory disease will ultimately have to come from clinical trials evaluating the different strategies discussed above. Selective α7nAChR agonists are currently evaluated as potential therapeutic drugs for the treatment of cognitive impairments in schizophrenia and Alzheimer's disease.110–114 To date, however, only a very limited number of studies have been performed to evaluate their anti-inflammatory potential in humans. "
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