References
- World Health Organization. Dementia 2019. [cited 2020 Sep 1]. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia
- M Wa Gm P, Ali GC, Wu YT, et al. World Alzheimer report 2015: the global impact of dementia: an analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International: London 2015.
- Alzheimer’s Association. Alzheimer’s disease facts and figures. Alzheimers Dement. 2020;16(3):391.
- World Health Organization. Infographic on dementia 2017. [cited 2020 Sep 1]. Available from: https://www.who.int/mental_health/neurology/dementia/infographic_dementia/en/
- Steinberg M, Shao H, Zandi P, et al. Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the cache county study. Int J Geriatr Psychiatry. 2008;23(2):170–177.
- Kales HC, Lyketsos CG, Miller EM, et al. Management of behavioral and psychological symptoms in people with alzheimer’s disease: an international delphi consensus. Int Psychogeriatr. 2019 Jan;31(1):83–90.
- Peters ME, Schwartz S, Han D, et al. Neuropsychiatric symptoms as predictors of progression to severe Alzheimer’s dementia and death: the cache county dementia progression study. Am J Psychiatry. 2015 May;172(5):460–465.
- Okura T, Plassman BL, Steffens DC, et al. Neuropsychiatric symptoms and the risk of institutionalization and death: the aging, demographics, and memory study. J Am Geriatr Soc. 2011;59(3):473–481.
- Cummings J, Mintzer J, Brodaty H, et al. Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition. Int Psychogeriatr. 2015;27(1):7–17.
- Kales HC, Gitlin LN, Lyketsos CG. Assessment and management of behavioral and psychological symptoms of dementia. BMJ. 2015;350(mar02 7):h369–h369.
- Millán-Calenti JC, Lorenzo-López L, Alonso-Búa B, et al. Optimal nonpharmacological management of agitation in Alzheimer’s disease: challenges and solutions. Clin Interv Aging. 2016;11:175–184.
- Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med. 2006 Oct 12;355(15):1525–1538.
- Sultzer DL, Davis SM, Tariot PN, et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer’s disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry. 2008;165(7):844–854.
- Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry. 2006 Mar;14(3):191–210.
- Yan J FDA extends black-box warning to all antipsychotics. PSYCHIATRIC NEWS 2008. [cited 2020 Sep 1]. Available from: https://psychnews.psychiatryonline.org/doi/full/10.1176/pn.43.14.0001
- Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543–546. 2016/05/01
- Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. Jama. 2014 Feb 19;311(7):682–691.
- Olin JT, Fox LS, Pawluczyk S, et al. A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with Alzheimer disease. Am J Geriatr Psychiatry. 2001 Fall;;9(4):400–405.
- Meyer RP, Schuyler D. Calming the agitated demented patient. Prim Care Companion CNS Disord. 2015;17(1):10.4088/PCC.15f01779.
- Baillon SF, Narayana U, Luxenberg JS, et al. Valproate preparations for agitation in dementia. Cochrane Database Syst Rev. 2018;10(10):CD003945–CD003945.
- Defrancesco M, Marksteiner J, Fleischhacker WW, et al. Use of benzodiazepines in Alzheimer’s Disease: a systematic review of literature. Int J Neuropsychopharmacol. 2015;18(10):pyv055–pyv055.
- Herrmann N, Ruthirakuhan M, Gallagher D, et al. Randomized placebo-controlled trial of nabilone for agitation in Alzheimer’s Disease. Am J Geriatr Psychiatry. 2019 Nov;27(11):1161–1173.
- Intracellular therapies. Intra-cellular therapies announces update on ITI-007–201 clinical trial for treatment of agitation in patients with probable alzheimer’s disease 2018. [cited 2020 Sep 1]. Available from: https://ir.intracellulartherapies.com/news-releases/news-release-details/intra-cellular-therapies-announces-update-iti-007-201-clinical
- Caraci F, Santagati M, Caruso G, et al. New antipsychotic drugs for the treatment of agitation and psychosis in Alzheimer’s disease: focus on brexpiprazole and pimavanserin. F1000Res. 2020;9:F1000. Faculty Rev–686
- Walker M. AXS-05 Alzheimer’s News Today 2020. [cited 2020 Sep 1]. Available from: https://alzheimersnewstoday.com/axs–05/
- Cummings JL, Lyketsos CG, Peskind ER, et al. Effect of dextromethorphan-quinidine on agitation in patients with alzheimer disease dementia: a randomized clinical trial. JAMA. 2015 Sep 22–29;314(12):1242–1254.
- Garay RP, Grossberg GTAVP. 786 for the treatment of agitation in dementia of the Alzheimer’s type. Expert Opin Investig Drugs. 2017 Jan;26(1):121–132.
- US. FDA Drug Approval package: Nuedexta (dextromethorphan hydrobromide and quinidine sulfate) Capsules 2011. [cited 2020 Sep 1]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/021879Orig1s000TOC.cfm
- Yang LP, Deeks ED. Dextromethorphan/quinidine: a review of its use in adults with pseudobulbar affect. Drugs. 2015 Jan;75(1):83–90.
- Concert pharmaceuticals achieves $2 million milestone from Avanir pharmaceuticals for phase 3 initiation of AVP-786 for agitation in patients with alzheimer’s disease 2015. [cited 2020 Sep 1]. Available from: https://ir.concertpharma.com/news-releases/news-release-details/concert-pharmaceuticals-achieves-2-million-milestone-avanir
- Fava M. The promise and challenges of drug repurposing in psychiatry. World Psychiatry. 2018;17(1):28–29.
- Avanir Pharmaceuticals Inc. Avanir pharmaceuticals announces initiation of phase III trial of AVP-786 for agitation in patients with Alzheimer’s Disease 2015. [cited 2020 Sep 1]. Available from: https://www.prnewswire.com/news-releases/avanir-pharmaceuticals-announces-initiation-of-phase-iii-trial-of-avp-786-for-agitation-in-patients-with-alzheimers-disease-300178893.html
- Taylor CP, Traynelis SF, Siffert J, et al. Pharmacology of dextromethorphan: relevance to dextromethorphan/quinidine (Nuedexta®) clinical use. Pharmacol Ther. 2016 2016/08/01/;164:170–182.
- National Center for Biotechnology Information. PubChem compound summary for CID 5360696, Dextromethorphan. [cited 2020 Aug 10]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Dextromethorphan
- National Center for Biotechnology Information. PubChem compound summary for CID 441074, Quinidine. [cited 2020 Aug 18]. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Quinidine
- Nguyen L, Robson MJ, Healy JR, et al. Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan. Plos One. 2014;9(2):e89985.
- Klein M, Musacchio JM. High affinity dextromethorphan binding sites in guinea pig brain. Effect of sigma ligands and other agents. J Pharmacol Exp Ther. 1989 Oct;251(1):207–215.
- Netzer R, Pflimlin P, Trube G. Dextromethorphan blocks N-methyl-D-aspartate-induced currents and voltage-operated inward currents in cultured cortical neurons. Eur J Pharmacol. 1993 Jul 20;238(2–3):209–216.
- Nguyen L, Thomas KL, Lucke-Wold BP, et al. Dextromethorphan: an update on its utility for neurological and neuropsychiatric disorders. Pharmacol Ther. 2016 Mar;159:1–22.
- Kachur JF, Morgan DW, Gaginella TS. Effect of dextromethorphan on guinea pig ileal contractility in vitro: comparison with levomethorphan, loperamide and codeine. J Pharmacol Exp Ther. 1986;239(3):661.
- Redwine KE, Trujillo KA. Effects of NMDA receptor antagonists on acute mu-opioid analgesia in the rat. Pharmacol Biochem Behav. 2003 Sep;76(2):361–372.
- Carr BC. Efficacy, abuse, and toxicity of over-the-counter cough and cold medicines in the pediatric population. Curr Opin Pediatr. 2006 Apr;18(2):184–188.
- Vavers E, Zvejniece L, Maurice T, et al. Allosteric modulators of sigma-1 receptor: a review [review]. Front Pharmacol. 2019 [2019Mar19];10:223.
- Hayashi T, Su TP. Sigma-1 receptor ligands: potential in the treatment of neuropsychiatric disorders. CNS Drugs. 2004;18(5):269–284.
- Brown C, Fezoui M, Selig WM, et al. Antitussive activity of sigma-1 receptor agonists in the guinea-pig. Br J Pharmacol. 2004;141(2):233–240.
- Nguyen L, Robson MJ, Healy JR, et al. Involvement of sigma-1 receptors in the antidepressant-like effects of dextromethorphan. PloS One. 2014;9(2):e89985–e89985.
- Shin EJ, Nah SY, Chae JS, et al. Dextromethorphan attenuates trimethyltin-induced neurotoxicity via sigma1 receptor activation in rats. Neurochem Int. 2007 May;50(6):791–799.
- Shin E-J, Nah S-Y, Kim W-K, et al. The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via sigma1 receptor activation: comparison with the effects of dextromethorphan. Br J Pharmacol. 2005;144(7):908–918.
- Church J, Jones MG, Davies SN, et al. Antitussive agents as N-methylaspartate antagonists: further studies. Can J Physiol Pharmacol. 1989 Jun;67(6):561–567.
- Kamel IR, Wendling WW, Chen D, et al. N-methyl-D-aspartate (NMDA) antagonists–S(+)-ketamine, dextrorphan, and dextromethorphan–act as calcium antagonists on bovine cerebral arteries. J Neurosurg Anesthesiol. 2008 Oct;20(4):241–248.
- Olivares D, Deshpande VK, Shi Y, et al. N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer’s disease, vascular dementia and Parkinson’s disease. Curr Alzheimer Res. 2012;9(6):746–758.
- Wilcock GK, Ballard CG, Cooper JA, et al. Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer’s disease: a pooled analysis of 3 studies. J Clin Psychiatry. 2008 Mar;69(3):341–348.
- Lanctôt KL, Herrmann N, Mazzotta P. Role of serotonin in the behavioral and psychological symptoms of dementia. J Neuropsychiatry Clin Neurosci. 2001;13(1): 5–21.
- Codd EE, Shank RP, Schupsky JJ, et al. Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. J Pharmacol Exp Ther. 1995 Sep;274(3):1263–1270.
- Ahtee L. Dextromethorphan inhibits 5-hydroxytryptamine uptake by human blood platelets and decreases 5-hydroxyindoleacetic acid content in rat brain. J Pharm Pharmacol. 1975;27(3): 177–180.
- Kim H-S, Park I-S, Lim H-K, et al. NMDA receptor antagonists enhance 5-HT2 receptor-mediated behavior, head-twitch response, in PCPA-treated mice. Arch Pharm Res. 1999;22(2):113–118.
- Gannon M, Che P, Chen Y, et al. Noradrenergic dysfunction in Alzheimer’s disease. Front Neurosci. 2015;9:220.
- Herrmann N, Lanctôt KL, Khan LR. The role of norepinephrine in the behavioral and psychological symptoms of dementia. J Neuropsychiatry Clin Neurosci. 2004;16(3): 261–276.
- Sinclair JG. Dextromethorphan-monoamine oxidase inhibitor interaction in rabbits. J Pharm Pharmacol. 1973;25(10):803–808.
- Jain A, Sisodia J, Quinidine. StatPearls Publishing LLC. [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Apr. [Updated 28]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542193
- Abdul Manap R, Wright CE, Gregory A, et al. The antitussive effect of dextromethorphan in relation to CYP2D6 activity. Br J Clin Pharmacol. 1999;48(3):382–387.
- Tung R. The development of deuterium-containing drugs. Innovat Pharm Technol. 2010;32(32):24–28.
- Schmider J, Greenblatt DJ, Fogelman SM, et al. Metabolism of dextromethorphan in vitro: involvement of cytochromes P450 2D6 and 3A3/4, with a possible role of 2E1. Biopharm Drug Dispos. 1997 Apr;18(3):227–240.
- Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 2005;5(1):6–13.
- Burns JM, Boyer EW. Antitussives and substance abuse. Subst Abuse Rehabil. 2013;4:75–82.
- Chen ZR, Somogyi AA, Bochner F. Simultaneous determination of dextromethorphan and three metabolites in plasma and urine using high-performance liquid chromatography with application to their disposition in man. Ther Drug Monit. 1990;12(1): 97–104.
- Wu D, Otton SV, Kalow W, et al. Effects of route of administration on dextromethorphan pharmacokinetics and behavioral response in the rat. J Pharmacol Exp Ther. 1995 Sep;274(3):1431–1437.
- Yu A, Haining RL. Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: can dextromethorphan be used as a dual probe for both CTP2D6 and CYP3A activities? Drug Metab Dispos. 2001 Nov;29(11):1514–1520.
- Werling LL, Lauterbach EC, Calef U. Dextromethorphan as a potential neuroprotective agent with unique mechanisms of action. Neurologist. 2007 Sep;13(5):272–293.
- Pope LE, Khalil MH, Berg JE, et al. Pharmacokinetics of dextromethorphan after single or multiple dosing in combination with quinidine in extensive and poor metabolizers. J Clin Pharmacol. 2004 Oct;44(10):1132–1142.
- European Medicines Agency. Nuedexta (dextromethorphan/quinidine) 2013 [cited 2020 Sep 1]. Available from: https://www.ema.europa.eu/en/documents/assessment-report/nuedexta-epar-public-assessment-report_en.pdf
- Panitch HS, Thisted RA, Smith RA, et al. Randomized, controlled trial of dextromethorphan/quinidine for pseudobulbar affect in multiple sclerosis. Ann Neurol. 2006 May;59(5):780–787.
- Liu L, Collier AC, Link JM, et al. Modulation of P-glycoprotein at the human blood-brain barrier by quinidine or rifampin treatment: a positron emission tomography imaging study. Drug Metab Dispos. 2015;43(11):1795–1804.
- Avanir Pharmaceuticals Inc. Avanir Pharmaceuticals announces positive interim data from pharmacokinetic study with next generation compound AVP-786 2013. [cited 2020 Sep 1]. Available from: https://www.prnewswire.com/news-releases/avanir-pharmaceuticals-announces-positive-interim-data-from-pharmacokinetic-study-with-next-generation-compound-avp-786-190182801.html
- Harbeson RT. SL Deuterium medicinal chemistry: a new approach to drug discovery and development 2014 [cited 2020 Sep 1]. Available from: https://www.concertpharma.com/wp-content/uploads/2014/12/MedChemNews-0514.pdf
- Clinicaltrials.gov. NCT01787747: Pharmacokinetics (PK) and tolerability of AVP-786 in healthy volunteers 2013. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT01787747?term=AVP–786
- NCT02174835: a phase-1 study to assess the pharmacokinetics, safety and tolerability of AVP-786 in healthy volunteers 2014. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02174835
- NCT02336347: A phase 1 study comparing AVP-786 with AVP-923 2015. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02336347?term=NCT02336347&draw=2&rank=1
- NCT02402595: Drug interaction study between AVP-923 and Itraconazole and between AVP-786 and Itraconazole in healthy adult subejcts (DDI) 2015. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02402595?term=NCT02402595&draw=2&rank=1
- NCT02174822: A Phase 1, Drug interaction study between AVP-786 and Paroxetine and between AVP-786 and Duloxetine in healthy subjects 2014. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02174822?term=NCT02174822&draw=2&rank=1
- Hemeryck A, Belpaire FM. Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. Curr Drug Metab. 2002 Feb;3(1):13–37.
- FDA. CYMBALTA (duloxetine hydrochloride) delayed-release capsules 2007 [cited 2020 Sep 1]. Avaialble from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021427s009s011s013lbl.pdf
- NCT01584440: efficacy, safety and tolerability study of AVP-923 (Dextromethorphan/Quinidine) for treatment of symptoms of agitation in alzheimer’s patients 2014. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT01584440?term=NCT01584440&draw=2&rank=1
- NCT02534038: safety, tolerability and efficacy of AVP-786 for the treatment of disinhibition 2015. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02534038?term=NCT02534038&draw=2&rank=1
- NCT03420222: study to assess the efficacy, safety, and tolerability of AVP-786 for the treatment of intermittent explosive disorder 2018. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03420222?term=NCT03420222&draw=2&rank=1
- NCT02153502: efficacy, safety, and tolerability study of AVP-786 as an adjunctive therapy in patients with major depressive disorder with an inadequate response to antidepressant treatment 2016. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02153502?term=NCT02153502&draw=2&rank=1
- NCT02477670: efficacy, safety, and tolerability of AVP-786 for the treatment of residual schizophrenia 2017. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02477670?term=NCT02477670&draw=2&rank=1
- NCT03095066: study to assess the efficacy, safety, and tolerability of AVP-786 for the treatment of neurobehavioral disinhibition including aggression, agitation, and irritability in patients with traumatic brain injury 2017. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03095066?term=NCT03095066&draw=2&rank=1
- NCT03896945: efficacy, safety, and tolerability of AVP-786 for the treatment of negative symptoms of schizophrenia 2019. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03896945?term=NCT03896945&draw=2&rank=1
- NCT02442765: efficacy, safety and tolerability of AVP-786 for the treatment of agitation in patients with dementia of the alzheimer’s type 2019. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02442765?term=NCT02442765&draw=2&rank=1
- Payesko J Avanir reports phase 3 data of AVP-786 for agitation in alzheimer disease 2019. [cited 2020 Sep 1]. Available from: https://www.neurologylive.com/clinical-focus/avanir-reports-phase-3-data-avp786-agitation-alzheimer
- NCT02442778: efficacy, safety, and tolerability of AVP-786 for the treatment of agitation in patients with dementia of the alzheimer’s type. 2019.
- Pharmaceuticals A, Inc. Avanir Pharmaceuticals reports data from the second phase 3 study evaluating investigational AVP-786 for the Treatment of moderate-to-severe agitation in patients with alzheimer’s dementia 2019. [cited 2020 Sep 1]. Available from: https://www.avanir.com/press/avanir-pharmaceuticals-inc-reports-data-second-phase-3-study-evaluating-investigational-avp
- NCT03393520: assessment of the efficacy, safety, and tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the treatment of agitation in patients with dementia of the alzheimer’s type. 2020.
- NCT02446132: long term, extension study of the safety and efficacy of AVP-786 for the treatment of agitation in patients with dementia of the alzheimer’s type 2020. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT02446132?term=NCT02446132&draw=2&rank=1
- NCT04408755: assessment of the efficacy, safety, and tolerability of AVP-786 for the treatment of agitation in patients with dementia of the alzheimer’s type 2020. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT04408755?term=NCT04408755&draw=2&rank=1
- NCT04464564: study to assess the efficacy, safety, and tolerability of AVP-786 for the treatment of agitation in patients with dementia of the alzheimer’s type 2020. [cited 2020 Sep 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT04464564?term=NCT04464564&draw=2&rank=1
- Bem JL, Dextromethorphan PR. An overview of safety issues. Drug Saf. 1992 May-Jun;7(3):190–199.
- Martinak B, Bolis RA, Black JR, et al. Dextromethorphan in cough syrup: the poor man’s psychosis. Psychopharmacol Bull. 2017 Sep 15;47(4):59–63.
- Ching MS, Blake CL, Ghabrial H, et al. Potent inhibition of yeast-expressed CYP2D6 by dihydroquinidine, quinidine, and its metabolites. Biochem Pharmacol. 1995 Sep 7;50(6):833–837.
- Schoedel KA, Morrow SA, Sellers EM. Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect. Neuropsychiatr Dis Treat. 2014;10:1161–1174.
- Timmins GS. Deuterated drugs; updates and obviousness analysis. Expert Opin Ther Pat. 2017 Dec;27(12):1353–1361.
- Fogel DB. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: a review. Contemp Clin Trials Commun. 2018;11:156–164.
- Pretorius SM, Phase GA. III trial failures: costly, but preventable. Applied Clinical Trials 2016;25:8.
- Fava M, Evins AE, Dorer DJ, et al. The problem of the placebo response in clinical trials for psychiatric disorders: culprits, possible remedies, and a novel study design approach. Psychother Psychosom. 2003 May-Jun;72(3):115–127.
- Boessen R, Knol MJ, Groenwold RH, et al. Increasing trial efficiency by early reallocation of placebo nonresponders in sequential parallel comparison designs: application to antidepressant trials. Clin Trials. 2012 Oct;9(5):578–587.
- Ballard C, Sharp S, Dextromethorphan CA. Quinidine for treating agitation in patients with alzheimer disease dementia. Jama. 2015;314(12):1233–1235.
- O’Gorman C, Khoury R, Anderson A, et al. A framework for developing pharmacotherapy for agitation in alzheimer’s disease: recommendations of the ISCTM working group. J Prev Alzheimer’s Dis. 2020;4(7):274-282.
- Cummings JL, Siffert J. Dextromethorphan-Quinidine for agitation in alzheimer disease–reply. Jama. 2016 Mar 15;315(11):1166–1167.
- Dineley KT, Pandya AA, Yakel JL. Nicotinic ACh receptors as therapeutic targets in CNS disorders. Trends Pharmacol Sci. 2015;36(2):96–108.