Alpha-7 nicotinic receptor explained

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.

Further, recent work has implicated this receptor as being important for generation of adult mammal neurons in the retina.^[2] Functional α7 receptors are present in the submucous plexus neurons of the guinea-pig ileum.^[3]

Medical relevance

Recent work has demonstrated a potential role in reducing inflammatory neurotoxicity in stroke, myocardial infarction, sepsis, and Alzheimer's disease.^{[4] [5] [6]}

An α7 nicotinic agonist appears to have positive effects on neurocognition in persons with schizophrenia.^[7]

Activation of α7 nicotinic acetylcholine receptor on mast cells, is a mechanism by which nicotine enhances atherosclerosis.^[8]

Both α4β2 and α7 nicotinic receptors appear to be critical for memory, working memory, learning, and attention.^[9]

α7-nicotinic receptors also appear to be involved in cancer progression. They have been shown to mediate cancer cell proliferation and metastasis.^[10] α7 receptors are also involved in angiogenic and neurogenic activity, and have anti-apoptotic effects.^{[11] [12] [13]}

Ligands

Agonists

• (+)-N-(1-azabicyclo[2.2.2]oct-3-yl)benzo[''b'']furan- 2-carboxamide: potent and highly subtype-selective^[14]
• Tilorone.
• A-582941: partial agonist; activates ERK1/2 and CREB phosphorylation; enhances cognitive performance^[15]
• AR-R17779: full agonist, nootropic
• Amyloid beta: neurotoxic marker of Alzheimer's disease^[16]
• TC-1698: subtype-selective; neuroprotective effects via activation of the JAK2/PI-3K cascade, neutralized by angiotensin II AT(2) receptor activation^[17]
• Bradanicline - partial agonist, in development for treatment of schizophrenia
• Encenicline - partial agonist with nootropic properties, in development for treatment of schizophrenia and Alzheimer's disease ^{[18] [19]}
• GTS-21 - partial agonist, in development for treatment of schizophrenia and/or Alzheimer's disease
• PHA-543,613 - selective and potent agonist with nootropic properties ^{[20] [21]}
• PNU-282,987 - selective and potent agonist, but may cause long QT syndrome
• PHA-709829: potent and subtype-selective; robust in vivo efficacy in a rat auditory sensory gating model^[22]
  • Analogues: improved hERG safety profile over PNU-282,987^[23]
• SSR-180,711

partial agonist^[24]

• Tropisetron: subtype-selective partial agonist; 5-HT₃ receptor antagonist^[25]
• WAY-317,538 - selective potent full agonist with nootropic and neuroprotective properties
• Anabasine
• Acetylcholine
• Nicotine
• Epiboxidine^[26]
• Choline^[27]
• ICH-3: subtype-selective partial agonist^[28]

Positive allosteric modulators (PAMs)

At least two types of positive allosteric modulators (PAMs) can be distinguished.^[29]

• PNU-120,596^[30]
• NS-1738: marginal effects on α₇ desensitization kinetics; modestly brain-penetrant^[31]
• 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^[32] In clinical development for cognitive deficits in schizophrenia.
• A-867744^{[33] [34]}
• Ivermectin

Other

• Nefiracetam^{[35] [36] [37]}

Antagonists

It is found that anandamide and ethanol cause an additive inhibition on the function of α₇-receptor by interacting with distinct regions of the receptor. Although ethanol inhibition of the α₇-receptor is likely to involve the N-terminal region of the receptor, the site of action for anandamide is located in the transmembrane and carboxyl-terminal domains of the receptors.^[38]

• Anandamide
• α-Bungarotoxin
• α-Conotoxin ArIB[V11L,V16D]: potent and highly subtype-selective; slowly reversible^[39]
• β-Caryophyllene^[40]
• Bupropion (very weakly)
• Dehydronorketamine
• Ethanol
• Hydroxybupropion (very weakly)
• Hydroxynorketamine
• Ketamine
• Kynurenic acid
• Memantine
• Lobeline
• Methyllycaconitine
• Norketamine
• Quinolizidine (−)-1-epi-207I: α₇ subtype preferring blocker^[41]

See also

• α3β2-Nicotinic receptor
• α3β4-Nicotinic receptor
• α4β2-Nicotinic receptor
• RIC3, a chaperone protein for α7 receptors
• Endocannabinoids

Notes and References

1. Pharmacology, (Rang, Dale, Ritter & Moore,, 5th ed., Churchill Livingstone 2003) p. 138.
2. Webster MK, Cooley-Themm CA, Barnett JD, Bach HB, Vainner JM, Webster SE, Linn CL . Evidence of BrdU-positive retinal neurons after application of an Alpha7 nicotinic acetylcholine receptor agonist . Neuroscience . 346 . 437–446 . March 2017 . 28147247 . 5341387 . 10.1016/j.neuroscience.2017.01.029 .
3. Glushakov AV, Voytenko LP, Skok MV, Skok V . Distribution of neuronal nicotinic acetylcholine receptors containing different alpha-subunits in the submucosal plexus of the guinea-pig . Autonomic Neuroscience . 110 . 1 . 19–26 . January 2004 . 14766321 . 10.1016/j.autneu.2003.08.012 . 25872540 .
4. Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ . 6 . Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit . Science . 334 . 6052 . 98–101 . October 2011 . 21921156 . 4548937 . 10.1126/science.1209985 . 2011Sci...334...98R .
5. Tracey KJ . Physiology and immunology of the cholinergic antiinflammatory pathway . The Journal of Clinical Investigation . 117 . 2 . 289–96 . February 2007 . 17273548 . 1783813 . 10.1172/JCI30555 .
6. Norman GJ, Morris JS, Karelina K, Weil ZM, Zhang N, Al-Abed Y, Brothers HM, Wenk GL, Pavlov VA, Tracey KJ, Devries AC . 6 . Cardiopulmonary arrest and resuscitation disrupts cholinergic anti-inflammatory processes: a role for cholinergic α7 nicotinic receptors . The Journal of Neuroscience . 31 . 9 . 3446–52 . March 2011 . 21368056 . 10.1523/JNEUROSCI.4558-10.2011 . 3758544 .
7. Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kem WR, Freedman R . 6 . Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia . Archives of General Psychiatry . 63 . 6 . 630–8 . June 2006 . 16754836 . 10.1001/archpsyc.63.6.630 . free .
8. Wang. Chen. Chen. Han. Zhu. Wei. Xu. Yinchuan. Liu. Mingfei. Zhu. Lianlian. Yang. Fan. Zhang. Ling. Liu. Xianbao. January 2017. Nicotine Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 37. 1. 53–65. 10.1161/ATVBAHA.116.307264. 1524-4636. 27834689. free.
9. Levin ED, McClernon FJ, Rezvani AH . Nicotinic effects on cognitive function: behavioral characterization, pharmacological specification, and anatomic localization . Psychopharmacology . 184 . 3–4 . 523–39 . March 2006 . 16220335 . 10.1007/s00213-005-0164-7 . 17166624 .
10. Dasgupta P, Rizwani W, Pillai S, Kinkade R, Kovacs M, Rastogi S, Banerjee S, Carless M, Kim E, Coppola D, Haura E, Chellappan S . 6 . Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines . International Journal of Cancer . 124 . 1 . 36–45 . January 2009 . 18844224 . 2826200 . 10.1002/ijc.23894 .
11. Brown KC, Lau JK, Dom AM, Witte TR, Luo H, Crabtree CM, Shah YH, Shiflett BS, Marcelo AJ, Proper NA, Hardman WE, Egleton RD, Chen YC, Mangiarua EI, Dasgupta P . 6 . MG624, an α7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway . Angiogenesis . 15 . 1 . 99–114 . March 2012 . 22198237 . 10.1007/s10456-011-9246-9 . 17889977 .
12. Wang J, Lu Z, Fu X, Zhang D, Yu L, Li N, Gao Y, Liu X, Yin C, Ke J, Li L, Zhai M, Wu S, Fan J, Lv L, Liu J, Chen X, Yang Q, Wang J . 6 . Alpha-7 Nicotinic Receptor Signaling Pathway Participates in the Neurogenesis Induced by ChAT-Positive Neurons in the Subventricular Zone . Translational Stroke Research . 8 . 5 . 484–493 . May 2017 . 28551702 . 5704989 . 10.1007/s12975-017-0541-7 .
13. Gergalova G, Lykhmus O, Kalashnyk O, Koval L, Chernyshov V, Kryukova E, Tsetlin V, Komisarenko S, Skok M . 6 . Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca2+ accumulation and cytochrome c release: study on isolated mitochondria . PLOS ONE . 7 . 2 . e31361 . 2012 . 22359587 . 3281078 . 10.1371/journal.pone.0031361 . 2012PLoSO...731361G . free .
14. Mazurov A, Klucik J, Miao L, Phillips TY, Seamans A, Schmitt JD, Hauser TA, Johnson RT, Miller C . 2-(Arylmethyl)-3-substituted quinuclidines as selective alpha 7 nicotinic receptor ligands . Bioorganic & Medicinal Chemistry Letters . 15 . 8 . 2073–7 . April 2005 . 15808471 . 10.1016/j.bmcl.2005.02.045 .
15. Tietje KR, Anderson DJ, Bitner RS, Blomme EA, Brackemeyer PJ, Briggs CA, Browman KE, Bury D, Curzon P, Drescher KU, Frost JM, Fryer RM, Fox GB, Gronlien JH, Håkerud M, Gubbins EJ, Halm S, Harris R, Helfrich RJ, Kohlhaas KL, Law D, Malysz J, Marsh KC, Martin RL, Meyer MD, Molesky AL, Nikkel AL, Otte S, Pan L, Puttfarcken PS, Radek RJ, Robb HM, Spies E, Thorin-Hagene K, Waring JF, Ween H, Xu H, Gopalakrishnan M, Bunnelle WH . 6 . Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties . CNS Neuroscience & Therapeutics . 14 . 1 . 65–82 . 2008 . 18482100 . 10.1111/j.1527-3458.2008.00037.x . 6494002 .
16. Talantova M, Sanz-Blasco S, Zhang X, Xia P, Akhtar MW, Okamoto S, Dziewczapolski G, Nakamura T, Cao G, Pratt AE, Kang YJ, Tu S, Molokanova E, McKercher SR, Hires SA, Sason H, Stouffer DG, Buczynski MW, Solomon JP, Michael S, Powers ET, Kelly JW, Roberts A, Tong G, Fang-Newmeyer T, Parker J, Holland EA, Zhang D, Nakanishi N, Chen HS, Wolosker H, Wang Y, Parsons LH, Ambasudhan R, Masliah E, Heinemann SF, Piña-Crespo JC, Lipton SA . 6 . Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss . Proceedings of the National Academy of Sciences of the United States of America . 110 . 27 . E2518–27 . July 2013 . 23776240 . 3704025 . 10.1073/pnas.1306832110 . 2013PNAS..110E2518T . free .
17. Marrero MB, Papke RL, Bhatti BS, Shaw S, Bencherif M . The neuroprotective effect of 2-(3-pyridyl)-1-azabicyclo[3.2.2]nonane (TC-1698), a novel alpha7 ligand, is prevented through angiotensin II activation of a tyrosine phosphatase . The Journal of Pharmacology and Experimental Therapeutics . 309 . 1 . 16–27 . April 2004 . 14722323 . 10.1124/jpet.103.061655 . 10.1.1.420.2457 . 7730290 .
18. Preskorn SH, Gawryl M, Dgetluck N, Palfreyman M, Bauer LO, Hilt DC . Normalizing effects of EVP-6124, an α-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia . Journal of Psychiatric Practice . 20 . 1 . 12–24 . January 2014 . 24419307 . 10.1097/01.pra.0000442935.15833.c5 . 19669958 .
19. Web site: Archived copy . 2014-03-13 . https://web.archive.org/web/20130319084417/http://www.envivopharma.com/pdf/EVP-6124AAICPressConf.pdf . 2013-03-19 . dead .
20. Sadigh-Eteghad S, Talebi M, Mahmoudi J, Babri S, Shanehbandi D . Selective activation of α7 nicotinic acetylcholine receptor by PHA-543613 improves Aβ25-35-mediated cognitive deficits in mice . Neuroscience . 298 . 81–93 . July 2015 . 25881725 . 10.1016/j.neuroscience.2015.04.017 . 22477612 .
21. Bali ZK, Inkeller J, Csurgyók R, Bruszt N, Horváth H, Hernádi I . Differential effects of α7 nicotinic receptor agonist PHA-543613 on spatial memory performance of rats in two distinct pharmacological dementia models . Behavioural Brain Research . 278 . 404–10 . February 2015 . 25447295 . 10.1016/j.bbr.2014.10.030 . 10791918 .
22. Acker BA, Jacobsen EJ, Rogers BN, Wishka DG, Reitz SC, Piotrowski DW, Myers JK, Wolfe ML, Groppi VE, Thornburgh BA, Tinholt PM, Walters RR, Olson BA, Fitzgerald L, Staton BA, Raub TJ, Krause M, Li KS, Hoffmann WE, Hajos M, Hurst RS, Walker DP . 6 . Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor: in vitro and in vivo activity . Bioorganic & Medicinal Chemistry Letters . 18 . 12 . 3611–5 . June 2008 . 18490160 . 10.1016/j.bmcl.2008.04.070 .
23. Walker DP, Wishka DG, Piotrowski DW, Jia S, Reitz SC, Yates KM, Myers JK, Vetman TN, Margolis BJ, Jacobsen EJ, Acker BA, Groppi VE, Wolfe ML, Thornburgh BA, Tinholt PM, Cortes-Burgos LA, Walters RR, Hester MR, Seest EP, Dolak LA, Han F, Olson BA, Fitzgerald L, Staton BA, Raub TJ, Hajos M, Hoffmann WE, Li KS, Higdon NR, Wall TM, Hurst RS, Wong EH, Rogers BN . 6 . Design, synthesis, structure-activity relationship, and in vivo activity of azabicyclic aryl amides as alpha7 nicotinic acetylcholine receptor agonists . Bioorganic & Medicinal Chemistry . 14 . 24 . 8219–48 . December 2006 . 17011782 . 10.1016/j.bmc.2006.09.019 .
24. Biton B, Bergis OE, Galli F, Nedelec A, Lochead AW, Jegham S, Godet D, Lanneau C, Santamaria R, Chesney F, Léonardon J, Granger P, Debono MW, Bohme GA, Sgard F, Besnard F, Graham D, Coste A, Oblin A, Curet O, Vigé X, Voltz C, Rouquier L, Souilhac J, Santucci V, Gueudet C, Françon D, Steinberg R, Griebel G, Oury-Donat F, George P, Avenet P, Scatton B . 6 . SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (1) binding and functional profile . Neuropsychopharmacology . 32 . 1 . 1–16 . January 2007 . 17019409 . 10.1038/sj.npp.1301189 . free .
25. Macor JE, Gurley D, Lanthorn T, Loch J, Mack RA, Mullen G, Tran O, Wright N, Gordon JC . 6 . The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist . Bioorganic & Medicinal Chemistry Letters . 11 . 3 . 319–21 . February 2001 . 11212100 . 10.1016/S0960-894X(00)00670-3 .
26. Dallanoce C, Matera C, De Amici M, Rizzi L, Pucci L, Gotti C, Clementi F, De Micheli C . The enantiomers of epiboxidine and of two related analogs: synthesis and estimation of their binding affinity at α4β2 and α7 neuronal nicotinic acetylcholine receptors . Chirality . 24 . 7 . 543–51 . July 2012 . 22566097 . 10.1002/chir.22052 .
27. Book: González-Rubio . Juana M . Choline as a tool to evaluate nicotinic receptor function in chromaffin cells. . Rojo . Jonathan . Tapia . Laura . Maneu . Victoria . Mulet . José . Valor . Luis M. . Criado . Manuel . Sala . Francisco . García . Antonio G. . Cell Biology of the Chromaffin Cell . Instituto Teófilo Hernando . Luis Gandía . 2004 . Borges . R. . Spain . Gandía . L..
28. Dallanoce C, Magrone P, Matera C, Frigerio F, Grazioso G, De Amici M, Fucile S, Piccari V, Frydenvang K, Pucci L, Gotti C, Clementi F, De Micheli C . 6 . Design, synthesis, and pharmacological characterization of novel spirocyclic quinuclidinyl-Δ2-isoxazoline derivatives as potent and selective agonists of α7 nicotinic acetylcholine receptors . ChemMedChem . 6 . 5 . 889–903 . May 2011 . 21365765 . 10.1002/cmdc.201000514 . 21407917 .
29. Grønlien JH, Håkerud M, Ween H, Thorin-Hagene K, Briggs CA, Gopalakrishnan M, Malysz J . Distinct profiles of alpha7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes . Molecular Pharmacology . 72 . 3 . 715–24 . September 2007 . 17565004 . 10.1124/mol.107.035410 . 2460247 .
30. Hurst RS, Hajós M, Raggenbass M, Wall TM, Higdon NR, Lawson JA, Rutherford-Root KL, Berkenpas MB, Hoffmann WE, Piotrowski DW, Groppi VE, Allaman G, Ogier R, Bertrand S, Bertrand D, Arneric SP . 6 . A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization . The Journal of Neuroscience . 25 . 17 . 4396–405 . April 2005 . 15858066 . 10.1523/JNEUROSCI.5269-04.2005 . 6725110 . free .
31. Timmermann DB, Grønlien JH, Kohlhaas KL, Nielsen EØ, Dam E, Jørgensen TD, Ahring PK, Peters D, Holst D, Christensen JK, Chrsitensen JK, Malysz J, Briggs CA, Gopalakrishnan M, Olsen GM . 6 . An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo . The Journal of Pharmacology and Experimental Therapeutics . 323 . 1 . 294–307 . October 2007 . 17625074 . 10.1124/jpet.107.120436 . 35392171 .
32. Ng HJ, Whittemore ER, Tran MB, Hogenkamp DJ, Broide RS, Johnstone TB, Zheng L, Stevens KE, Gee KW . 6 . Nootropic alpha7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators . Proceedings of the National Academy of Sciences of the United States of America . 104 . 19 . 8059–64 . May 2007 . 17470817 . 1876571 . 10.1073/pnas.0701321104 . 2007PNAS..104.8059N . free .
33. Faghih R, Gopalakrishnan SM, Gronlien JH, Malysz J, Briggs CA, Wetterstrand C, Ween H, Curtis MP, Sarris KA, Gfesser GA, El-Kouhen R, Robb HM, Radek RJ, Marsh KC, Bunnelle WH, Gopalakrishnan M . 6 . Discovery of 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a novel positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor . Journal of Medicinal Chemistry . 52 . 10 . 3377–84 . May 2009 . 19419141 . 10.1021/jm9003818 .
34. Malysz J, Grønlien JH, Anderson DJ, Håkerud M, Thorin-Hagene K, Ween H, Wetterstrand C, Briggs CA, Faghih R, Bunnelle WH, Gopalakrishnan M . 6 . In vitro pharmacological characterization of a novel allosteric modulator of alpha 7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744), exhibiting unique pharmacological profile . The Journal of Pharmacology and Experimental Therapeutics . 330 . 1 . 257–67 . July 2009 . 19389923 . 10.1124/jpet.109.151886 . 5470552 .
35. Nishizaki T, Nomura T, Matuoka T, Kondoh T, Enikolopov G, Enikolopo G, Sumikawa K, Watabe S, Shiotani T, Yoshii M . The anti-dementia drug nefiracetam facilitates hippocampal synaptic transmission by functionally targeting presynaptic nicotinic ACh receptors . Brain Research. Molecular Brain Research . 80 . 1 . 53–62 . August 2000 . 11039729 . 10.1016/S0169-328X(00)00117-0 .
36. Zhao X, Kuryatov A, Lindstrom JM, Yeh JZ, Narahashi T . Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons . Molecular Pharmacology . 59 . 4 . 674–83 . April 2001 . 11259610 . 10.1124/mol.59.4.674 . 27825145 .
37. Nishizaki T, Matsuoka T, Nomura T, Kondoh T, Watabe S, Shiotani T, Yoshii M . Presynaptic nicotinic acetylcholine receptors as a functional target of nefiracetam in inducing a long-lasting facilitation of hippocampal neurotransmission . Alzheimer Disease and Associated Disorders . 14 . S82–94 . 2000 . Suppl 1 . 10850735 . 10.1097/00002093-200000001-00013 . 25914087 .
38. Oz M, Jackson SN, Woods AS, Morales M, Zhang L . Additive effects of endogenous cannabinoid anandamide and ethanol on alpha7-nicotinic acetylcholine receptor-mediated responses in Xenopus Oocytes . The Journal of Pharmacology and Experimental Therapeutics . 313 . 3 . 1272–80 . June 2005 . 15687372 . 10.1124/jpet.104.081315 . 23201726 .
39. Whiteaker P, Christensen S, Yoshikami D, Dowell C, Watkins M, Gulyas J, Rivier J, Olivera BM, McIntosh JM . 6 . Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist . Biochemistry . 46 . 22 . 6628–38 . June 2007 . 17497892 . 10.1021/bi7004202 .
40. Sharma. Charu. Al Kaabi. Juma M.. Nurulain. Syed M.. Goyal. Sameer N.. Kamal. Mohammad Amjad. Ojha. Shreesh. 2016. Polypharmacological Properties and Therapeutic Potential of β-Caryophyllene: A Dietary Phytocannabinoid of Pharmaceutical Promise. Current Pharmaceutical Design. 22. 21. 3237–3264. 1873-4286. 26965491. 10.2174/1381612822666160311115226.
41. Tsuneki H, You Y, Toyooka N, Kagawa S, Kobayashi S, Sasaoka T, Nemoto H, Kimura I, Dani JA . 6 . Alkaloids indolizidine 235B', quinolizidine 1-epi-207I, and the tricyclic 205B are potent and selective noncompetitive inhibitors of nicotinic acetylcholine receptors . Molecular Pharmacology . 66 . 4 . 1061–9 . October 2004 . 15258256 . 10.1124/mol.104.000729 . 17490742 .