Recent advances in positive allosteric modulators of the AMPA receptor

Current Opinion in Drug Discovery and Development

Volumn 9, Issue 5, 2006, Pages 571-579

  Morrow, John A ^a   Maclean, John K F ^a   Jamieson, Craig ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

AMPA; Cognition; Glutamate; Positive allosteric modulator; Schizophrenia; X ray crystallography

Indexed keywords

2,3 DIHYDRO 3,4 CYCLOPENTANO 1,2,4 BENZOTHIADIAZINE 1,1 DIOXIDE; 6 QUINOXALINECARBOXYLIC ACID PIPERIDIDE; ALPHA AMINO 3 HYDROXY 5 METHYL 4 ISOXAZOLEPROPIONIC ACID; AMPA RECEPTOR; AMPA RECEPTOR AGONIST; AMPAKINE; ANIRACETAM; ATYPICAL ANTIPSYCHOTIC AGENT; BENZAMIDE; BENZAMIDE DERIVATIVE; BENZOTHIADIAZINE DERIVATIVE; BENZOXAZINE DERIVATIVE; CX 614; CX 717; CYCLOTHIAZIDE; FARAMPATOR; GLUTAMATE RECEPTOR; LY 404187; LY 451395; UNCLASSIFIED DRUG;

ALLOSTERISM; ATTENTION DEFICIT DISORDER; CLINICAL TRIAL; COGNITIVE DEFECT; DRUG BINDING; DRUG POTENCY; DRUG STRUCTURE; HUMAN; LEARNING; MEMORY; NERVE CELL PLASTICITY; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SCHIZOPHRENIA; SHORT TERM MEMORY; STRUCTURE ANALYSIS;

ANIMALS; HUMANS; MODELS, MOLECULAR; RECEPTORS, AMPA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33748612166     PISSN: 13676733     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (45)

1. Mayer ML, Armstrong N: Structure and function of glutamate receptor ion channels. Annu Rev Physiol (2004) 66:161-181.
2. Kew JN, Kemp JA: Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berlin) (2005) 179(1):4-29.
3. Palmer CL, Cotton L, Henley JM: The molecular pharmacology and cell biology of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Pharmacol Rev (2005) 57(2):253-277. An excellent review of the biological properties of AMPA receptors.
4. Sun Y, Olson R, Horning M, Armstrong N, Mayer M, Gouaux E: Mechanism of glutamate receptor desensitization. Nature (2002) 417(6886):245-253. Describes the structure of cyclothiazide bound to the GluR2 receptor complex and provides evidence for the link between allosteric modulator binding and receptor desensitization.
5. Black MD: Therapeutic potential of positive AMPA modulators and their relationship to AMPA receptor subunits. A review of preclinical data. Psychopharmacology (Berlin) (2005) 179(1):154-163.
6. Lynch G: AMPA receptor modulators as cognitive enhancers. Curr Opin Pharmacol (2004) 4(1):4-11.
7. Lynch G: Glutamate-based therapeutic approaches: AMPAKINEs. Curr Opin Pharmacol (2006) 6(1):82-88.
8. O'Neill MJ, Bleakman D, Zimmerman DM, Nisenbaum ES: AMPA receptor potentiators for the treatment of CNS disorders. Curr Drug Targets-CNS Neurol Disord (2004) 3(3):181-194.
9. Danysz W: Positive modulators of AMPA receptors as a potential treatment for schizophrenia. Curr Opin Invest Drugs (2002) 3(7):1062-1066.
10. Porrino U, Daunais JB, Rogers GA, Hampson RE, Deadwyler SA: Facilitation of task performance and removal of the effects of sleep deprivation by an AMPAKINE (CX717) in nonhuman primates. PLoS Biol (2005) 3(9):e299 Describes evidence that the AMPAKINE CX-717 reverses cognitive deficits and normalizes disturbances in cortical activity in monkeys as a result of sleep deprivation.
11. Millan MJ: N-Methyl-D-aspartate receptors as a target for improved antipsychotic agents: Novel insights and clinical perspectives. Psychopharmacology (Berlin) (2005) 179(1):30-53.
12. Lahti AC, Koffel B, LaPorte D, Tamminga CA: Subanesthetic doses of ketamine stimulate psychosis In schizophrenia. Neuropsychopharmacology (1995) 13(1):9-19.
13. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS: Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry (1994) 51(3):199-214.
14. Larson J, Quach CN, LeDuc BQ, Nguyen A, Rogers GA, Lynch G: Effects of an AMPA receptor modulator on methamphetamine-induced hyperactivity in rats. Brain Res (1996) 738(2):353-356.
15. Johnson SA, Luu NT, Herbst TA, Knapp R, Lutz D, Arai A, Rogers GA, Lynch G: Synergistic interactions between AMPAKINEs and antipsychotic drugs. J Pharmacol Exp Ther (1999) 289(1):392-397.
16. Goff DC, Leahy L, Berman I, Posever T, Herz L, Leon AC, Johnson SA, Lynch G: A placebo-controlled pilot study of the AMPAKINE CX516 added to clozapine in schizophrenia. J Clin Psychopharmacol (2001) 21(5):484-487.
17. Marenco S, Egan MF, Goldberg TE, Knable MB, McClure RK, Winterer G, Weinberger DR: Preliminary experience with an AMPAKINE (CX516) as a single agent for the treatment of schizophrenia: A case series. Schizophr Res (2002) 57(2-3):221-226
18. Li X, Tizzano JP, Griffey K, Clay M, Lindstrom T, Skolnick P: Antidepressant-like actions of an AMPA receptor potentiator (LY392098). Neuropharmacology (2001) 40(8):1028-1033.
19. Li X, Witkin JM, Need AB, Skolnick P: Enhancement of antidepressant potency by a potentiator of AMPA receptors. Cell Mol Neurobiol (2003) 23(3):419-430.
20. Legutko B, Li X, Skolnick P: Regulation of BDNF expression in primary neuron culture by LY392098, a novel AMPA receptor potentiator. Neuropharmacology (2001) 40(8):1019-1027.
21. Mackowiak M, O'Neill MJ, Hicks CA, Bleakman D, Skolnick P: An AMPA receptor potentiator modulates hippocampal expression of BDNF: An in vivo study. Neuropharmacology (2002) 43(1):1-10.
22. Bai F, Bergeron M, Nelson DL: Chronic AMPA receptor potentiator (LY451646) treatment increases cell proliferation in adult rat hippocampus. Neuropharmacology (2003) 44(8):1013-1021.
23. Dicou E, Rangon CM, Guimiot F, Spedding M, Gressens P: Positive allosteric modulators of AMPA receptors are neuroprotective against lesions induced by an NMDA agonist in neonatal mouse brain. Brain Res (2003) 970(1-2):221-225.
24. Murray TK, Whalley K, Robinson CS, Ward MA, Hicks CA, Lodge D, Vandergriff JL, Baumbarger P, Siuda E, Gates M, Ogden AM et al: LY503430, a novel α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor potentiator with functional, neuroprotective and neurotrophic effects in rodent models of Parkinson's disease. J Pharmacol Exp Ther (2003) 306(2):752-762.
25. O'Neill MJ, Murray TK, Whalley K, Ward MA, Hicks CA, Woodhouse S, Osborne DJ, Skolnick P: Neurotrophic actions of the novel AMPA receptor potentiator, LY404187, In rodent models of Parkinson's disease. Eur J Pharmacol (2004) 486(2):163-174.
26. Gainetdinov RR, Mohn AR, Bohn LM, Caron MG: Glutamatergic modulation of hyperactivity in mice lacking the dopamine transporter. Proc Natl Acad Sci USA (2001) 98(20):11047-11054.
27. Ito I, Tanabe S, Kohda A, Sugiyama H: Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam. J Physiol (1990) 424:533-543.
28. Arai AC, Xia YF, Rogers G, Lynch G, Kessler M: Benzamide-type AMPA receptor modulators form two subfamilies with distinct modes of action. J Pharmacol Exp Ther (2002) 303(3):1075-1085.
29. Arai AC, Kessler M, Rogers G, Lynch G: Effects of the potent AMPAKINE CX614 on hippocampal and recombinant AMPA receptors: Interactions with cyclothiazide and GYKI 52466. Mol Pharmacol (2000) 58(4):802-813.
30. Lynch G, Granger R, Ambros-Ingerson J, Davis CM, Kessler M, Schehr R: Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans. Exp Neurol (1997) 145(1):89-92.
31. Pirotte B, Podona T, Diouf O, de Tullio P, Lebrun P, Dupont L, Somers F, Delarge J, Morain P, Lestage P, Lepagnol J et al: 4H-1,2,4-Pyridothiadiazine 1,1-dioxides and 2,3-dihydro-4H-1,2, 4-pyridothiadiazine 1,1-dioxides chemically related to diazoxide and cyclothiazide as powerful positive allosteric modulators of (R/S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid receptors: Design, synthesis, pharmacology, and structure-activity relationships. J Med Chem (1998) 41(16):2946-2959.
32. Desos P, Serkiz B, Morain P, Lepagnol J, Cordi A: Enantioselective synthesis of a pyrrolo-benzothiadiazine derivative S 18986, a new AMPA receptor positive modulator. Bioorg Med Chem Lett (1996) 6(24):3003-3008.
33. Lebrun C, Pilliere E, Lestage P: Effects of S 18986-1, a novel cognitive enhancer, on memory performances In an object recognition task in rats. Eur J Pharmacol (2000) 401(2):205-212.
34. Omstein PL, Zimmerman DM, Arnold MB, Bleisch TJ, Cantrell B, Simon R, Zarrinmayeh H, Baker SR, Gates M, Tizzano JP, Bleakman D et al: Biarylpropylsulfonamides as novel, potent potentiators of 2-amino-3-(5-methyl-3- hydroxyisoxazol-4-yl)-propanoic acid (AMPA) receptors. J Med Chem (2000) 43(23):4354-4358. Details of the discovery AMPA positive modulators with significantly improved efficacy through high-throughput screening and subsequent hit optimization.
35. Quirk JC, Nisenbaum ES: LY404187: A novel positive allosteric modulator of AMPA receptors. CNS Drug Rev (2002) 8(3):255-282.
36. 3H]N-2-(4-(N- Benzamido)phenyl)propyl-2-propanesulfonamide: A novel AMPA receptor potentiator and radioligand. J Med Chem (2001) 44(3):302-304.
37. Jhee SS, Chappell AS, Zarotsky V, Moran SV, Rosenthal M, Kim E, Chalon S, Toublanc N, Brandt J, Coutant DE, Ereshefsky L: Multiple-dose plasma pharmacokinetic and safety study of LY450108 and LY451395 (AMPA receptor potentiators) and their concentration in cerebrospinal fluid in healthy human subjects. J Clin Pharmacol (2006) 46(4):424-432.
38. Shepherd TA, Aikins JA, Bleakman D, Cantrell BE, Rearick JP, Simon RL, Smith EC, Stephenson GA, Zimmerman DM, Mandelzys A, Jarvie KR et al: Design and synthesis of a novel series of 1,2-disubstituted cyclopentanes as small, potent potentiators of 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA) receptors. J Med Chem (2002) 45(10):2101-2111. Optimization of the initial lead compounds in the sulfonamide series of AMPA receptor positive allosteric modulators to furnish analogs with improved potency compared to the progenitor compounds.
39. Armstrong N, Sun Y, Chen GQ, Gouaux E: Structure of a glutamate-receptor ligand-binding core in complex with kainate. Nature (1998) 395(6705):913-917.
40. Chen PE, Wyllie DJ: Pharmacological insights obtained from structure-function studies of ionotropic glutamate receptors. Br J Pharmacol (2006) 147(8):839-853.
41. 702 is an important determinant of agonist binding and domain closure of the ligand-binding core of GluR2. Mol Pharmacol (2005) 67(3):703-713.
42. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res (2000) 28(1):235-242.
43. Jin R, Clark S, Weeks AM, Dudman JT, Gouaux E, Partin KM: Mechanism of positive allosteric modulators acting on AMPA receptors. J Neurosci (2005) 25(39):9027-9036. Describes the structures of the aniracetam- and CX-614-bound GluR2 receptor complexes and provides evidence for differentiation of the structural determinants for receptor desensitization and deactivation.
44. Quirk JC, Nisenbaum ES. Multiple molecular determinants for allosteric modulation of alternatively spliced AMPA receptors. J Neurosci (2003) 23(34):10953-10962.
45. Horning MS, Mayer ML: Regulation of AMPA receptor gating by ligand binding core dimers. Neuron (2004) 41(3):379-388.