Clozapine and olanzapine improve insufficient inhibitory processing of the P20-N40 auditory evoked potential: Evidence for a nicotinic mechanism

Simosky, Johanna K.; Stevens, Karen E.; Adler, Lothar; Freedman, Robert

doi:10.1016/s0920-9964(03)80395-x

Cited by 1 publication

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“…These results suggest that increased release of acetylcholine from the 5HT 3 blockade may be targeting nicotinic receptors. In support of this hypothesis, other 5HT 3 blockers such as olanzapine (Simosky et al, 2003) and tropisetron (Koike et al, 2005; Zhang et al, 2012) also normalize P50 sensory processing. Currently, little is known about the pharmacology of α7nAChRs containing the CHRFAM7A subunit, dupα7.…”

Section: 0 Drug Developmentmentioning

confidence: 75%

The human CHRNA7 and CHRFAM7A genes: A review of the genetics, regulation, and function

et al. 2015

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The human α7 neuronal nicotinic acetylcholine receptor gene (CHRNA7) is ubiquitously expressed in both the central nervous system and in the periphery. CHRNA7 is genetically linked to multiple disorders with cognitive deficits, including schizophrenia, bipolar disorder, ADHD, epilepsy, Alzheimer’s disease, and Rett syndrome. The regulation of CHRNA7 is complex; more than a dozen mechanisms are known, one of which is a partial duplication of the parent gene. Exons 5-10 of CHRNA7 on chromosome 15 were duplicated and inserted 1.6 Mb upstream of CHRNA7, interrupting an earlier partial duplication of two other genes. The chimeric CHRFAM7A gene product, dupα7, assembles with α7 subunits, resulting in a dominant negative regulation of function. The duplication is human specific, occurring neither in primates nor in rodents. The duplicated α7 sequence in exons 5-10 of CHRFAM7A is almost identical to CHRNA7, and thus is not completely queried in high throughput genetic studies (GWAS). Further, pre-clinical animal models of the α7nAChR utilized in drug development research do not have CHRFAM7A (dupα7) and cannot fully model human drug responses. The wide expression of CHRNA7, its multiple functions and modes of regulation present challenges for study of this gene in disease.

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Section: 0 Drug Developmentmentioning

confidence: 75%