Alpha-7 nicotinic receptor

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Molecular model of the α7 nicotinic receptor.

The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long term memory, consisting entirely of α7 subunits.[1] As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].

It is located in the brain, spleen, and lymphocytes of lymph nodes where activation yields post- and presynaptic excitation,[1] mainly by increased Ca2+ permeability.

Medical relevance[edit]

Recent work has demonstrated a potential role in reducing inflammatory neurotoxicity in stroke, myocardial infarction, sepsis, and alzheimers disease.[2][3][4]

An α7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia.[5]

Both α4β2 and α7 nicotinic receptors appear to be critical for memory, working memory, learning, and attention.[6]

α7-nicotinic receptors also appear to be involved in cancer progression. They have been shown to mediate cancer cell proliferation and metastasis.[7] α7 receptors are also involved in angiogenic activity, and have anti-apoptotic effects.[8][9]

Ligands[edit]

Agonists[edit]

Positive Allosteric Modulators (PAMs)[edit]

At least two types of positive allosteric modulators (PAMs) can be distinguished.[21]

  • PNU-120,596[22]
  • NS-1738: marginal effects on α7 desensitization kinetics; modestly brain-penetrant[23]
  • AVL-3288: unlike the above PAMs, AVL-3288 does not affect α7 desensitization kinetics, and is readily brain penetrant. Improves cognitive behavior in animal models[24] In clinical development for cognitive deficits in schizophrenia.
  • A-867744[25][26]
  • Ivermectin
  • Galantamine

Other[edit]

Antagonists[edit]

  • α-conotoxin ArIB[V11L,V16D]: potent and highly subtype-selective; slowly reversible[30]
  • Memantine
  • Quinolizidine (–)-1-epi-207I: α7 subtype preferring blocker[31]

See also[edit]

References[edit]

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  3. ^ Tracey, KJ (2007). "Physiology and immunology of the cholinergic antiinflammatory pathway". The Journal of clinical investigation 117 (2): 289–96. doi:10.1172/JCI30555. PMC 1783813. PMID 17273548. 
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