Augmentation of cognitive function by NS9283, a stoichiometry-dependent positive allosteric modulator of α2- and α4-containing nicotinic acetylcholine receptors

British Journal of Pharmacology

Volumn 167, Issue 1, 2012, Pages 164-182

  Timmermann, D B ^a   Sandager Nielsen, K ^a   Dyhring, T ^a   Smith, M ^a   Jacobsen, A M ^a   Nielsen, E O ^a   Grunnet, M ^a   Christensen, J K ^a   Peters, D ^a   Kohlhaas, K ^b   Olsen, G M ^a   Ahring, P K ^a  

^a NEUROSEARCH A S   (Denmark)

^b ABBOTT LABORATORIES   (United States)

Author keywords

4 nACh receptors; 2 nACh receptors; allosteric modulation; cognitive dysfunction; Nicotinic acetylcholine receptors; therapeutics

Indexed keywords

3 [3 (3 PYRIDYL) 1,2,4 OXADIAZOL 5 YL]BENZONITRILE; CALCIUM ION; MECAMYLAMINE; NICOTINIC RECEPTOR; NICOTINIC RECEPTOR ALPHA2; NICOTINIC RECEPTOR ALPHA2BETA2; NICOTINIC RECEPTOR ALPHA2BETA4; NICOTINIC RECEPTOR ALPHA4; NICOTINIC RECEPTOR ALPHA4BETA4; NOOTROPIC AGENT; NS 9283; UNCLASSIFIED DRUG;

ALLOSTERISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; ATTENTION; BRAIN CELL; BRAIN ELECTROPHYSIOLOGY; COGNITION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG HALF LIFE; DRUG MECHANISM; DRUG MEGADOSE; DRUG METABOLISM; EPISODIC MEMORY; EVOKED RESPONSE; FLUORESCENCE ANALYSIS; IN VITRO STUDY; IN VIVO STUDY; MALE; MAMMAL CELL; MAZE TEST; MENTAL PERFORMANCE; MENTAL TASK; MOUSE; NEUROMODULATION; NONHUMAN; OOCYTE; PREPULSE INHIBITION; PRIORITY JOURNAL; RAT; REFERENCE MEMORY; RESPONSE TIME; SENSORY NERVE CONDUCTION; STOICHIOMETRY; THALAMOCORTICAL NEURON; TIME TO MAXIMUM PLASMA CONCENTRATION; VOLTAGE CLAMP; XENOPUS;

ALLOSTERIC REGULATION; ANIMALS; CELL LINE; CELL LINE, TUMOR; COGNITION; FEMALE; HEK293 CELLS; HUMANS; MALE; MAZE LEARNING; MICE; MOTOR ACTIVITY; NICOTINE; NICOTINIC AGONISTS; OOCYTES; OXADIAZOLES; PROTEIN SUBUNITS; PYRIDINES; RATS; RATS, SPRAGUE-DAWLEY; RATS, WISTAR; RECEPTORS, NICOTINIC; RECOGNITION (PSYCHOLOGY); XENOPUS LAEVIS;

EID: 84864724117     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2012.01989.x     Document Type: Article

References (44)

1. Acri JB, Morse DE, Popke EJ, Grunberg NE, (1994). Nicotine increases sensory gating measured as inhibition of the acoustic startle reflex in rats. Psychopharmacology (Berl) 114: 369-374.
2. Albrecht BK, Berry V, Boezio AA, Cao L, Clarkin K, Guo W, et al,. (2008). Discovery and optimization of substituted piperidines as potent, selective, CNS-penetrant alpha4beta2 nicotinic acetylcholine receptor potentiators. Bioorg Med Chem Lett 18: 5209-5212.
3. Alexander SP, Mathie A, Peters JA, (2011). Guide to Receptors and Channels (GRAC), 5th edition. Br J Pharmacol 164 (Suppl. 1): S1-324.
4. Bitner RS, Bunnelle WH, Anderson DJ, Briggs CA, Buccafusco J, Curzon P, et al,. (2007). Broad-spectrum efficacy across cognitive domains by alpha7 nicotinic acetylcholine receptor agonism correlates with activation of ERK1/2 and CREB phosphorylation pathways. J Neurosci 27: 10578-10587.
5. Briggs CA, Gubbins EJ, Marks MJ, Putman CB, Thimmapaya R, Meyer MD, et al,. (2006). Untranslated region-dependent exclusive expression of high-sensitivity subforms of alpha4beta2 and alpha3beta2 nicotinic acetylcholine receptors. Mol Pharmacol 70: 227-240.
6. Cole BJ, Robbins TW, (1987). Amphetamine impairs the discriminative performance of rats with dorsal noradrenergic bundle lesions on a 5-choice serial reaction time task: new evidence for central dopaminergic-noradrenergic interactions. Psychopharmacology (Berl) 91: 458-466.
7. Decker MW, Majchrzak MJ, Anderson DJ, (1992). Effects of nicotine on spatial memory deficits in rats with septal lesions. Brain Res 572: 281-285.
8. Dunbar G, Demazieres A, Monreal A, Cisterni C, Metzger D, Kuchibhatla R, et al,. (2006). Pharmacokinetics and safety profile of ispronicline (TC-1734), a new brain nicotinic receptor partial agonist, in young healthy male volunteers. J Clin Pharmacol 46: 715-726.
9. Dunbar G, Boeijinga PH, Demazieres A, Cisterni C, Kuchibhatla R, Wesnes K, et al,. (2007a). Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers. Psychopharmacology (Berl) 191: 919-929.
10. Dunbar GC, Inglis F, Kuchibhatla R, Sharma T, Tomlinson M, Wamsley J, (2007b). Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI). J Psychopharmacol 21: 171-178.
11. Faghih R, Gopalakrishnan SM, Gronlien JH, Malysz J, Briggs CA, Wetterstrand C, et al,. (2009). 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. J Med Chem 52: 3377-3384.
12. Fenster CP, Beckman ML, Parker JC, Sheffield EB, Whitworth TL, Quick MW, et al,. (1999). Regulation of alpha4beta2 nicotinic receptor desensitization by calcium and protein kinase C. Mol Pharmacol 55: 432-443.
13. Gatto GJ, Bohme GA, Caldwell WS, Letchworth SR, Traina VM, Obinu MC, et al,. (2004). TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects. CNS Drug Rev 10: 147-166.
14. Gotti C, Zoli M, Clementi F, (2006). Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol Sci 27: 482-491.
15. Gotti C, Moretti M, Meinerz NM, Clementi F, Gaimarri A, Collins AC, et al,. (2008). Partial deletion of the nicotinic cholinergic receptor alpha 4 or beta 2 subunit genes changes the acetylcholine sensitivity of receptor-mediated 86Rb+ efflux in cortex and thalamus and alters relative expression of alpha 4 and beta 2 subunits. Mol Pharmacol 73: 1796-1807.
16. Grottick AJ, Haman M, Wyler R, Higgins GA, (2003). Reversal of a vigilance decrement in the aged rat by subtype-selective nicotinic ligands. Neuropsychopharmacology 28: 880-887.
17. Han ZY, Le Novere N, Zoli M, Hill JA, Jr, Champtiaux N, Changeux JP, (2000). Localization of nAChR subunit mRNAs in the brain of Macaca mulatta. Eur J Neurosci 12: 3664-3674.
18. Harpsøe K, Ahring PK, Christensen JK, Jensen ML, Peters D, Balle T, (2011). Unraveling the high- and low-sensitivity agonist responses of nicotinic acetylcholine receptors. J Neurosci 31: 10759-10766.
19. Hurst RS, Hajos M, Raggenbass M, Wall TM, Higdon NR, Lawson JA, et al,. (2005). A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization. J Neurosci 25: 4396-4405.
20. Ji J, Schrimpf MR, Sippy KB, Bunnelle WH, Li T, Anderson DJ, et al,. (2007). Synthesis and structure-activity relationship studies of 3,6-diazabicyclo[3.2.0]heptanes as novel alpha4beta2 nicotinic acetylcholine receptor selective agonists. J Med Chem 50: 5493-5508.
21. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, (2010). NC3Rs Reporting Guidelines Working Group. Br J Pharmacol 160: 1577-1579.
22. Khiroug SS, Khiroug L, Yakel JL, (2004). Rat nicotinic acetylcholine receptor alpha2beta2 channels: comparison of functional properties with alpha4beta2 channels in Xenopus oocytes. Neuroscience 124: 817-822.
23. Lee CH, Zhu C, Malysz J, Campbell T, Shaughnessy T, Honore P, et al,. (2011). alpha4beta2 neuronal nicotinic receptor positive allosteric modulation: an approach for improving the therapeutic index of alpha4beta2 nAChR agonists in pain. Biochem Pharmacol 82: 959-966.
24. Macdonald RL, Olsen RW, (1994). GABAA receptor channels. Annu Rev Neurosci 17: 569-602.
25. McGrath J, Drummond G, Kilkenny C, Wainwright C, (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160: 1573-1576.
26. Mirza NR, Stolerman IP, (1998). Nicotine enhances sustained attention in the rat under specific task conditions. Psychopharmacology (Berl) 138: 266-274.
27. Mirza NR, Larsen JS, Mathiasen C, Jacobsen TA, Munro G, Erichsen HK, et al,. (2008). NS11394 [3'-[5-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]- biphenyl-2-carbonitrile], a unique subtype-selective GABAA receptor positive allosteric modulator: in vitro actions, pharmacokinetic properties and in vivo anxiolytic efficacy. J Pharmacol Exp Ther 327: 954-968.
28. Nelson ME, Kuryatov A, Choi CH, Zhou Y, Lindstrom J, (2003). Alternate stoichiometries of alpha4beta2 nicotinic acetylcholine receptors. Mol Pharmacol 63: 332-341.
29. Ng HJ, Whittemore ER, Tran MB, Hogenkamp DJ, Broide RS, Johnstone TB, et al,. (2007). Nootropic alpha7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators. Proc Natl Acad Sci USA 104: 8059-8064.
30. Parikh V, Kozak R, Martinez V, Sarter M, (2007). Prefrontal acetylcholine release controls cue detection on multiple timescales. Neuron 56: 141-154.
31. Rezvani AH, Levin ED, (2001). Cognitive effects of nicotine. Biol Psychiatry 49: 258-267.
32. Riekkinen M, Riekkinen P, Jr, (1994). Effects of THA and physostigmine on spatial navigation and avoidance performance in mecamylamine and PCPA-treated rats. Exp Neurol 125: 111-118.
33. Rowbotham MC, Duan WR, Thomas J, Nothaft W, Backonja MM, (2009). A randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of ABT-594 in patients with diabetic peripheral neuropathic pain. Pain 146: 245-252.
34. Socci DJ, Sanberg PR, Arendash GW, (1995). Nicotine enhances Morris water maze performance of young and aged rats. Neurobiol Aging 16: 857-860.
35. Springer SK, Woodin KS, Berry V, Boezio AA, Cao L, Clarkin K, et al,. (2008). Synthesis and activity of substituted carbamates as potentiators of the alpha4beta2 nicotinic acetylcholine receptor. Bioorg Med Chem Lett 18: 5643-5647.
36. Taly A, Corringer PJ, Guedin D, Lestage P, Changeux JP, (2009). Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system. Nat Rev Drug Discov 8: 733-750.
37. Timmermann DB, Grønlien JH, Kohlhaas KL, Nielsen EO, Dam E, Jørgensen TD, et al,. (2007). An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther 323: 294-307.
38. Wada E, Wada K, Boulter J, Deneris E, Heinemann S, Patrick J, et al,. (1989). Distribution of alpha 2, alpha 3, alpha 4, and beta 2 neuronal nicotinic receptor subunit mRNAs in the central nervous system: a hybridization histochemical study in the rat. J Comp Neurol 284: 314-335.
39. Weltzin MM, Schulte MK, (2010). Pharmacological characterization of the allosteric modulator desformylflustrabromine and its interaction with alpha4beta2 neuronal nicotinic acetylcholine receptor orthosteric ligands. J Pharmacol Exp Ther 334: 917-926.
40. Whiteaker P, Wilking JA, Brown RW, Brennan RJ, Collins AC, Lindstrom JM, et al,. (2009). Pharmacological and immunochemical characterization of alpha2* nicotinic acetylcholine receptors (nAChRs) in mouse brain. Acta Pharmacol Sin 30: 795-804.
41. Yu KD, Liu Q, Wu J, Lukas RJ, (2009). Kinetics of desensitization and recovery from desensitization for human alpha4beta2-nicotinic acetylcholine receptors stably expressed in SH-EP1 cells. Acta Pharmacol Sin 30: 805-817.
42. Zhou Y, Nelson ME, Kuryatov A, Choi C, Cooper J, Lindstrom J, (2003). Human alpha4beta2 acetylcholine receptors formed from linked subunits. J Neurosci 23: 9004-9015.
43. Zhu CZ, Chin CL, Rustay NR, Zhong C, Mikusa J, Chandran P, et al,. (2011). Potentiation of analgesic efficacy but not side effects: co-administration of an alpha4beta2 neuronal nicotinic acetylcholine receptor agonist and its positive allosteric modulator in experimental models of pain in rats. Biochem Pharmacol 82: 967-976.
44. Zoli M, Le Novere N, Hill JA, Jr, Changeux JP, (1995). Developmental regulation of nicotinic ACh receptor subunit mRNAs in the rat central and peripheral nervous systems. J Neurosci 15: 1912-1939.