Group i and group II metabotropic glutamate receptor allosteric modulators as novel potential antipsychotics

Current Opinion in Pharmacology

Volumn 20, Issue , 2015, Pages 40-45

  Walker, Adam G ^a   Conn, P Jeffrey ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADX 71149; ARIPIPRAZOLE; EGLUMETAD; METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR 1 AGONIST; METABOTROPIC RECEPTOR 2 AGONIST; METABOTROPIC RECEPTOR 3 AGONIST; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR 5 AGONIST; METABOTROPIC RECEPTOR AGONIST; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NEUROLEPTIC AGENT; OLANZAPINE; RISPERIDONE; UNCLASSIFIED DRUG; METABOTROPIC GLUTAMATE RECEPTOR TYPE 1; METABOTROPIC RECEPTOR; METABOTROPIC RECEPTOR 2; METABOTROPIC RECEPTOR 3;

ARTICLE; BINDING SITE; CONVULSION; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DRUG TOLERABILITY; HUMAN; LONG TERM DEPRESSION; LONG TERM POTENTIATION; NEGATIVE SYNDROME; NERVE CELL NECROSIS; NERVE CELL PLASTICITY; NONHUMAN; PHASE 2 CLINICAL TRIAL (TOPIC); POSITIVE SYNDROME; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION; ALLOSTERISM; ANIMAL; DRUG DESIGN; DRUG EFFECTS; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOPHYSIOLOGY; SCHIZOPHRENIA;

ALLOSTERIC REGULATION; ANIMALS; ANTIPSYCHOTIC AGENTS; DRUG DESIGN; HUMANS; MOLECULAR TARGETED THERAPY; RECEPTORS, METABOTROPIC GLUTAMATE; SCHIZOPHRENIA;

EID: 84912115050     PISSN: 14714892     EISSN: 14714973     Source Type: Journal    
DOI: 10.1016/j.coph.2014.11.003     Document Type: Review

References (59)

1. D.A. Lewis, and J.A. Lieberman Catching up on schizophrenia: natural history and neurobiology Neuron 28 2000 325 334
2. J.A. Lieberman Effectiveness of antipsychotic drugs in patients with chronic schizophrenia: efficacy, safety and cost outcomes of CATIE and other trials J Clin Psychiatry 68 2007 e04
3. J.H. Krystal Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses Arch Gen Psychiatry 51 1994 199 214
4. J. Coyle Glutamate and schizophrenia beyond the dopamine hypothesis Cell Mol Neurobiol 26 2006 363 382
5. D.C. Javitt Glutamatergic theories of schizophrenia Isr J Psychiatry Relat Sci 47 2010 4 16
6. P.J. Conn, and J.P. Pin Pharmacology and functions of metabotropic glutamate receptors Annu Rev Pharmacol Toxicol 37 1997 205 237
7. P.J. Conn, A. Christopoulos, and C.W. Lindsley Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders Nat Rev Drug Discov 8 2009 41 54
8. P.J. Conn, C.W. Lindsley, and C.K. Jones Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia Trends Pharmacol Sci 30 2009 25 31
9. M.J. Marino, and P.J. Conn Direct and indirect modulation of the N-methyl d-aspartate receptor Curr Drug Targets CNS Neurol Disord 1 2002 1 16
10. M.D. Ehlers Synapse structure: glutamate receptors connected by the shanks Curr Biol 9 1999 R848 R850
11. G. Mannaioni Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function J Neurosci 21 2001 5925 5934
12. A.J. Doherty A novel: competitive mGlu(5) receptor antagonist (LY344545) blocks DHPG-induced potentiation of NMDA responses but not the induction of LTP in rat hippocampal slices Br J Pharmacol 131 2000 239 244
13. H. Awad Activation of metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus J Neurosci 20 2000 7871 7879
14. S.A. Brody Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors Mol Psychiatry 9 2004 35 41
15. G.G. Kinney Metabotropic glutamate subtype 5 receptors modulate locomotor activity and sensorimotor gating in rodents J Pharmacol Exp Ther 306 2003 116 123
16. U.C. Campbell The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates PCP-induced cognitive deficits in rats Psychopharmacology (Berl) 175 2004 310 318
17. S.R. Stauffer Progress toward positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGlu5) ACS Chem Neurosci 2 2011 450 470
18. G.G. Kinney A novel selective positive allosteric modulator of metabotropic glutamate receptor subtype 5 has in vivo activity and antipsychotic-like effects in rat behavioral models J Pharmacol Exp Ther 313 2005 199 206
19. F. Liu ADX47273 [S-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]-oxadiazol-5-yl]-piperidin-1-yl}-methanone]: a novel metabotropic glutamate receptor 5-selective positive allosteric modulator with preclinical antipsychotic-like and procognitive activities J Pharmacol Exp Ther 327 2008 827 839
20. A.L. Rodriguez Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity Mol Pharmacol 78 2010 1105 1123
21. C. Schlumberger Comparison of the mGlu5 receptor positive allosteric modulator ADX47273 and the mGlu2/3 receptor agonist LY354740 in tests for antipsychotic-like activity Eur J Pharmacol 623 2009 73 83
22. J.D. Vardigan MK-801 produces a deficit in sucrose preference that is reversed by clozapine, d-serine, and the metabotropic glutamate 5 receptor positive allosteric modulator CDPPB: relevance to negative symptoms associated with schizophrenia? Pharmacol Biochem Behav 95 2010 223 229
23. J.E. Ayala mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning Neuropsychopharmacology 34 2009 2057 2071
24. M.J. Noetzel Functional impact of allosteric agonist activity of selective positive allosteric modulators of mGlu5 in regulating CNS function Mol Pharmacol 2012
25. S. Parmentier-Batteur Mechanism based neurotoxicity of mGlu5 positive allosteric modulators - development challenges for a promising novel antipsychotic target Neuropharmacology 82 2014 161 173
26. J.M. Rook Unique signaling profiles of positive allosteric modulators of metabotropic glutamate receptor subtype 5 determine differences in in vivo activity Biol Psychiatry 73 2013 501 509
27. A. Ghoshal Stimulus bias of metabotropic glutamate receptor 5 allosteric modulators - impact on CNS effects and implications for use as therapeutic agents Neuroscience 2013 San Diego, CA 2013
28. R.K. Wong Group I mGluR-induced epileptogenesis: distinct and overlapping roles of mGluR1 and mGluR5 and implications for antiepileptic drug design Epilepsy Curr 5 2005 63 68
29. M.A. Ayoub Deleterious GRM1 mutations in Schizophrenia PLOS ONE 7 2012 e32849
30. D.W. Volk, S.M. Eggan, and D.A. Lewis Alterations in metabotropic glutamate receptor 1 alpha and regulator of G protein signaling 4 in the prefrontal cortex in schizophrenia Am J Psychiatry 167 2010 1489 1498
31. H.P. Cho Chemical modulation of mutant mGlu1 receptors derived from deleterious GRM1 mutations found in schizophrenics ACS Chem Biol 2014
32. A. Satow Unique antipsychotic activities of the selective metabotropic glutamate receptor 1 allosteric antagonist 2-cyclopropyl-5-[1-(2-fluoro-3-pyridinyl)-5-methyl-1H-1,2,3-triazol-4-yl]-2,3-dihydro-1H-isoindol-1-one J Pharmacol Exp Ther 330 2009 179 190
33. A. Satow Pharmacological effects of the metabotropic glutamate receptor 1 antagonist compared with those of the metabotropic glutamate receptor 5 antagonist and metabotropic glutamate receptor 2/3 agonist in rodents: detailed investigations with a selective allosteric metabotropic glutamate receptor 1 antagonist, FTIDC [4-[1-(2-Fluoropyridine-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide] J Pharmacol Exp Ther 326 2008 577 586
34. B. Moghaddam, and B.W. Adams Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats Science 281 1998 1349 1352
35. J. Cartmell, J.A. Monn, and D.D. Schoepp The metabotropic glutamate 2/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus d-amphetamine motor behaviors in rats J Pharmacol Exp Ther 291 1999 161 170
36. D.S. Lorrain Group II mGlu receptor activation suppresses norepinephrine release in the ventral hippocampus and locomotor responses to acute ketamine challenge Neuropsychopharmacology 28 2003 1622 1632
37. D.S. Lorrain Effects of ketamine and N-methyl-d-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268 Neuroscience 117 2003 697 706
38. H. Homayoun, M.E. Jackson, and B. Moghaddam Activation of metabotropic glutamate 2/3 receptors reverses the effects of NMDA receptor hypofunction on prefrontal cortex unit activity in awake rats J Neurophysiol 93 2005 1989 2001
39. C. Trepanier Group II metabotropic glutamate receptors modify N-methyl-d-aspartate receptors via Src kinase Sci Rep 3 2013 926
40. J. Cheng SNARE proteins are essential in the potentiation of NMDA receptors by group II metabotropic glutamate receptors J Physiol 591 2013 3935 3947
41. J.P. Tyszkiewicz Group II metabotropic glutamate receptors enhance NMDA receptor currents via a protein kinase C-dependent mechanism in pyramidal neurones of rat prefrontal cortex J Physiol 554 2004 765 777
42. B.J. Kinon, and J.C. Gomez Clinical development of pomaglumetad methionil: a non-dopaminergic treatment for schizophrenia Neuropharmacology 66 2013 82 86
43. S.T. Patil Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial Nat Med 13 2007 1102 1107
44. D.H. Adams A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia BMC Psychiatry 13 2013 143
45. Lilly Lilly Stops Phase III Development of Pomaglumetad Methionil for the Treatment of Schizophrenia Based on Efficacy Results 2012 Available from: https://investor.lilly.com/releasedetail.cfm?ReleaseID=703018
46. W.P. Spooren Lack of effect of LY314582 (a group 2 metabotropic glutamate receptor agonist) on phencyclidine-induced locomotor activity in metabotropic glutamate receptor 2 knockout mice Eur J Pharmacol 397 2000 R1 R2
47. M.J. Fell Evidence for the role of metabotropic glutamate (mGlu)2 not mGlu3 receptors in the preclinical antipsychotic pharmacology of the mGlu2/3 receptor agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039) J Pharmacol Exp Ther 326 2008 209 217
48. P.N. Vinson, and P.J. Conn Metabotropic glutamate receptors as therapeutic targets for schizophrenia Neuropharmacology 62 2012 1461 1472
49. R. Galici A selective allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors has effects similar to an orthosteric mGlu2/3 receptor agonist in mouse models predictive of antipsychotic activity J Pharmacol Exp Ther 315 2005 1181 1187
50. R. Galici Biphenyl-indanone A, a positive allosteric modulator of the metabotropic glutamate receptor subtype 2, has antipsychotic- and anxiolytic-like effects in mice J Pharmacol Exp Ther 318 2006 173 185
51. M. Bennyworth A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis Mol Pharmacol 72 2007 477 484
52. S. Urwyler Allosteric modulation of family C G-protein-coupled receptors: from molecular insights to therapeutic perspectives Pharmacol Rev 63 2011 59 126
53. M.P. Johnson Metabotropic glutamate 2 receptor potentiators: receptor modulation, frequency-dependent synaptic activity, and efficacy in preclinical anxiety and psychosis model(s) Psychopharmacology (Berl) 179 2005 271 283
54. P.J. Harrison The group II metabotropic glutamate receptor 3 (mGluR3, mGlu3, GRM3): expression, function and involvement in schizophrenia J Psychopharmacol 22 2008 308 322
55. Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci Nature 511 2014 421 427
56. A. Jablensky Polymorphisms associated with normal memory variation also affect memory impairment in schizophrenia Genes Brain Behav 10 2011 410 417
57. B.T. Baune Association between genetic variants of the metabotropic glutamate receptor 3 (GRM3) and cognitive set shifting in healthy individuals Genes Brain Behav 9 2010 459 466
58. R. Fujioka Comprehensive behavioral study of mGluR3 knockout mice: implication in schizophrenia related endophenotypes Mol Brain 7 2014 31
59. M. Lainiola, C. Procaccini, and A.-M. Linden mGluR3 knockout mice show a working memory defect and an enhanced response to MK-801 in the T- and Y-maze cognitive tests Behav Brain Res 266 2014 94 103