In vivo pharmacological characterization of the structurally novel, potent, selective mGlu2/3 receptor agonist LY404039 in animal models of psychiatric disorders

Psychopharmacology

Volumn 193, Issue 1, 2007, Pages 121-136

  Rorick Kehn, Linda M ^a   Johnson, Bryan G ^a   Knitowski, Karen M ^a   Salhoff, Craig R ^a   Witkin, Jeffrey M ^a   Perry, Kenneth W ^a   Griffey, Kelly I ^a   Tizzano, Joseph P ^b   Monn, James A ^a   McKinzie, David L ^a   Schoepp, Darryle D ^a  

^a ELI LILLY AND COMPANY   (United States)

^b DOV Pharmaceuticals   (United States)

Author keywords

Animal models; Antipsychotic; Anxiety; Anxiolytic; Metabotropic glutamate (mGlu) receptors; MGlu2 3 receptor agonist; Psychiatric disorders; Schizophrenia

Indexed keywords

AMPHETAMINE; DOPAMINE; LY 404039; METABOTROPIC RECEPTOR AGONIST; MONOAMINE; PHENCYCLIDINE; SEROTONIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANXIETY DISORDER; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACTIVITY; DRUG BIOAVAILABILITY; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG MECHANISM; IN VIVO STUDY; LOCOMOTION; MALE; MICRODIALYSIS; MOTOR DYSFUNCTION; NEUROTRANSMISSION; NONHUMAN; PREFRONTAL CORTEX; PRIORITY JOURNAL; PSYCHOSIS; RAT; ROTAROD TEST; TASK PERFORMANCE; TISSUE LEVEL; TRANQUILIZING ACTIVITY;

AMINO ACIDS; AMPHETAMINE; ANIMALS; BEHAVIOR, ANIMAL; BICYCLO COMPOUNDS, HETEROCYCLIC; CYCLIC S-OXIDES; DIAZEPAM; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; MALE; MENTAL DISORDERS; MICE; MOLECULAR STRUCTURE; MOTOR ACTIVITY; PHENCYCLIDINE; PREFRONTAL CORTEX; RATS; RATS, INBRED F344; RATS, SPRAGUE-DAWLEY; RECEPTORS, METABOTROPIC GLUTAMATE; XANTHENES;

EID: 34250162538     PISSN: 00333158     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00213-007-0758-3     Document Type: Article

References (54)

1. Ascher-Svanum H, Stensland MD, Kinon BJ, Tollefson GD (2005) Weight gain as a prognostic indicator of therapeutic improvement during acute treatment of schizophrenia with placebo or active antipsychotic. J Psychopharmacol 19:110-117
2. Bergink V, Westenberg HG (2005) Metabotropic glutamate II receptor agonists in panic disorder: a double blind clinical trial with LY354740. Int Clin Psychopharmacol 20:291-293
3. Bergink V, van Megen HJ, Westenberg HG (2004) Glutamate and anxiety. Eur Neuropsychopharmacol 14:175-183
4. Bueno AB, Collado I, de Dios A, Dominguez C, Martin JA, Martin LM, Martinez-Grau MA, Montero C, Pedregal C, Catlow J, Coffey DS, Clay MP, Dantzig AH, Lindstrom T, Monn JA, Jiang H, Schoepp DD, Stratford RE, Tabas LB, Tizzano JP, Wright RA, Herin MF (2005) Dipeptides as effective prodrugs of the unnatural amino acid (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic Acid (LY354740), a selective group II metabotropic glutamate receptor agonist. J Med Chem 48:5305-5320
5. Cartmell J, Monn JA, Schoepp DD (1999) The metabotropic glutamate 2/3 receptor agonists LY354740 and LY379268 selectively attenuate phencyclidine versus d-amphetamine motor behaviors in rats. J Pharmacol Exp Ther 291:161-170
6. Cartmell J, Schoepp DD (2000) Regulation of neurotransmitter release by metabotropic glutamate receptors. J Neurochem 75:889-907
7. Cartmell J, Perry KW, Salhoff CR, Monn JA, Schoepp DD (2000a) The potent, selective mGlu2/3 receptor agonist LY379268 increases extracellular levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindole-3-acetic acid in the medial prefrontal cortex of the freely moving rat. J Neurochem 75:1147-1154
8. Cartmell J, Salhoff CR, Perry KW, Monn JA, Schoepp DD (2000b) Dopamine and 5-HT turnover are increased by the mGlu2/3 receptor agonist LY379268 in rat medial prefrontal cortex, nucleus accumbens and striatum. Brain Res 887:378-384
9. Galici R, Echemendia NG, Rodriguez AL, Conn PJ (2005) 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 315:1181-1187
10. Goldman-Rakic PS (1999) The relevance of the dopamine-D1 receptor in the cognitive symptoms of schizophrenia. Neuropsychopharmacology 21:S170-S180
11. Grillon C, Cordova J, Levine LR, Morgan CA 3rd (2003) Anxiolytic effects of a novel group II metabotropic glutamate receptor agonist (LY354740) in the fear-potentiated startle paradigm in humans. Psychopharmacology (Berl) 168:446-454
12. Gudex C (1991) Adverse effects of benzodiazepines. Soc Sci Med 33:587-596
13. Helton DR, Tizzano JP, Monn JA, Schoepp DD, Kallman MJ (1997) LY354740: a metabotropic glutamate receptor agonist which ameliorates symptoms of nicotine withdrawal in rats. Neuropharmacology 36:1511-1516
14. Helton DR, Tizzano JP, Monn JA, Schoepp DD, Kallman MJ (1998) Anxiolytic and side-effect profile of LY354740: a potent, highly selective, orally active agonist for group II metabotropic glutamate receptors. J Pharmacol Exp Ther 284:651-660
15. Heresco-Levy U (2005) Glutamatergic neurotransmission modulators as emerging new drugs for schizophrenia. Expert Opin Emerg Drugs 10:827-844
16. Iijima M, Shimazaki T, Ito A, Chaki S (2007) Effects of metabotropic glutamate 2/3 receptor antagonists in the stress-induced hyperthermia test in singly housed mice. Psychopharmacology (Berl) 190:233-239
17. Johnson JT, Mattiuz EL, Chay SH, Herman JL, Wheeler WJ, Kassahun K, Swanson SP, Phillips DL (2002) The disposition, metabolism, and pharmacokinetics of a selective metabotropic glutamate receptor agonist in rats and dogs. Drug Metab Dispos 30:27-33
18. Johnson MP, Barda D, Britton TC, Emkey R, Hornback WJ, Jagdmann GE, McKinzie DL, Nisenbaum ES, Tizzano JP, Schoepp DD (2005) Metabotropic glutamate 2 receptor potentiators: receptor modulation, frequency-dependent synaptic activity, and efficacy in preclinical anxiety and psychosis model(s). Psychopharmacology (Berl) 179:271-283
19. Kellner M, Muhtz C, Stark K, Yassouridis A, Arlt J, Wiedemann K (2005) Effects of a metabotropic glutamate(2/3) receptor agonist (LY544344/LY354740) on panic anxiety induced by cholecystokinin tetrapeptide in healthy humans: preliminary results. Psychopharmacology (Berl) 179:310-315
20. Kingston AE, Ornstein PL, Wright RA, Johnson BG, Mayne NG, Burnett JP, Belagaje R, Wu S, Schoepp DD (1998) LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors. Neuropharmacology 37:1-12
21. Krystal JH, Abi-Saab W, Perry E, D'Souza DC, Liu N, Gueorguieva R, McDougall L, Hunsberger T, Belger A, Levine L, Breier A (2005a) Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects. Psychopharmacology (Berl) 179:303-309
22. Krystal JH, Perry Jr EB, Gueorguieva R, Belger A, Madonick SH, Abi-Dargham A, Cooper TB, Macdougall L, Abi-Saab W, D'Souza DC (2005b) Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch Gen Psychiatry 62:985-994
23. Li XM, Perry KW, Wong DT, Bymaster FP (1998) Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum. Psychopharmacology (Berl) 136:153-161
24. Linden A-M, Greene SJ, Bergeron M, Schoepp DD (2004) Anxiolytic activity of the mGlu2/3 receptor agonist LY354740 on the elevated plus maze is associated with the suppression of stress-induced c-Fos in the hippocampus and increases in c-Fos induction in several other stress-sensitive brain regions. Neuropsychopharmacology 29:502-513
25. Linden AM, Bergeron M, Schoepp DD (2005a) Comparison of c-Fos induction in the brain by the mGlu2/3 receptor antagonist LY341495 and agonist LY354740: evidence for widespread endogenous tone at brain mGlu2/3 receptors in vivo. Neuropharmacology 49(Suppl 1):120-134
26. Linden AM, Shannon H, Baez M, Yu JL, Koester A, Schoepp DD (2005b) Anxiolytic-like activity of the mGLU2/3 receptor agonist LY354740 in the elevated plus maze test is disrupted in metabotropic glutamate receptor 2 and 3 knock-out mice. Psychopharmacology (Berl) 179:284-291
27. Marek GJ, Wright RA, Schoepp DD, Monn JA, Aghajanian GK (2000) Physiological antagonism between 5-hydroxytryptamine(2A) and group II metabotropic glutamate receptors in prefrontal cortex. J Pharmacol Exp Ther 292:76-87
28. Moghaddam B (2002) Stress activation of glutamate neurotransmission in the prefrontal cortex: implications for dopamine-associated psychiatric disorders. Biol Psychiatry 51:775-787
29. Moghaddam B, Adams BW (1998) Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 281:1349-1352
30. Monn JA, Valli MJ, Massey SM, Wright RA, Salhoff CR, Johnson BG, Howe T, Alt CA, Rhodes GA, Robey RL, Griffey KR, Tizzano JP, Kallman MJ, Helton DR, Schoepp DD (1997) Design, synthesis, and pharmacological characterization of (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740): a potent, selective, and orally active group 2 metabotropic glutamate receptor agonist possessing anticonvulsant and anxiolytic properties. J Med Chem 40:528-537
31. Monn JA, Massey SM, Valli MJ, Henry SS, Stephenson GA, Bures M, Herin M, Catlow J, Giera D, Wright RA, Johnson BG, Andis SL, Kingston A, Schoepp DD (2007) Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: identification of potent, selective, and orally bioavailable agonists for mGlu2/3 receptors. J Med Chem 50:233-240
32. Morris BJ, Cochran SM, Pratt JA (2005) PCP: from pharmacology to modelling schizophrenia. Curr Opin Pharmacol 5:101-106
33. Nakazato A, Sakagami K, Yasuhara A, Ohta H, Yoshikawa R, Itoh M, Nakamura M, Chaki S (2004) Synthesis, in vitro pharmacology, structure-activity relationships, and pharmacokinetics of 3-alkoxy-2-amino-6-fluorobicyclo[3.1.0] hexane-2,6-dicarboxylic acid derivatives as potent and selective group II metabotropic glutamate receptor antagonists. J Med Chem 47:4570-4587
34. Ohishi H, Shigemoto R, Nakanishi S, Mizuno N (1993a) Distribution of the messenger RNA for a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat. Neuroscience 53:1009-1018
35. Ohishi H, Shigemoto R, Nakanishi S, Mizuno N (1993b) Distribution of the mRNA for a metabotropic glutamate receptor (mGluR3) in the rat brain: an in situ hybridization study. J Comp Neurol 335:252-266
36. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, New York
37. Rickels K, Rynn M (2002) Pharmacotherapy of generalized anxiety disorder. J Clin Psychiatry 63(Suppl 14):9-16
38. Rodd ZA, McKinzie DL, Bell RL, McQueen VK, Murphy JM, Schoepp DD, McBride WJ (2006) The metabotropic glutamate 2/3 receptor agonist LY404039 reduces alcohol-seeking but not alcohol self-administration in alcohol-preferring (P) rats. Behav Brain Res 171:207-215
39. Rorick-Kehn LM, Perkins EJ, Knitowski KM, Hart JC, Johnson BG, Schoepp DD, McKinzie DL (2006) Improved bioavailability of the mGlu2/3 receptor agonist LY354740 using a prodrug strategy: in vivo pharmacology of LY544344. J Pharmacol Exp Ther 316:905-913
40. Rorick-Kehn LM, Johnson BG, Burkey JL, Wright RA, Calligaro DO, Marek GJ, Nisenbaum ES, Catlow JT, Kingston AE, Giera DD, Herin MF, Monn JA, McKinzie DL, Schoepp DD (2007) Pharmacological and pharmacokinetic properties of a structurally-novel, potent, selective mGlu2/3 receptor agonist: in vitro characterization of LY404039. J Pharmacol Exp Ther (in press) DOI 10.1124/jpet.106.110809
41. Sachdev PS (2005) Neuroleptic-induced movement disorders: an overview. Psychiatr Clin North Am 28:255-274
42. Sams-Dodd F (1998) Effects of diazepam, citalopram, methadone and naloxone on PCP-induced stereotyped behaviour and social isolation in the rat social interaction test. Neurosci Biobehav Rev 23:287-293
43. Schoepp DD (2001) Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system. J Pharmacol Exp Ther 299:12-20
44. Schoepp DD, Marek GJ (2002) Preclinical pharmacology of mGlu2/3 receptor agonists: novel agents for schizophrenia? Curr Drug Targets CNS Neurol Disord 1:215-225
45. Schoepp DD, Wright RA, Levine LR, Gaydos B, Potter WZ (2003) LY354740, an mGlu2/3 receptor agonist as a novel approach to treat anxiety/stress. Stress 6:189-197
46. Schreiber R, Lowe D, Voerste A, De Vry J (2000) LY354740 affects startle responding but not sensorimotor gating or discriminative effects of phencyclidine. Eur J Pharmacol 388:R3-R4
47. Shekhar A, Keim SR (2000) LY354740, a potent group II metabotropic glutamate receptor agonist prevents lactate-induced panic-like response in panic-prone rats. Neuropharmacology 39:1139-1146
48. Spooren WP, Gasparini F, van der Putten H, Koller M, Nakanishi S, Kuhn R (2000) 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:R1-R2
49. Spooren WP, Schoeffter P, Gasparini F, Kuhn R, Gentsch C (2002) Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608). Eur J Pharmacol 435:161-170
50. Steinpreis RE, Anders KA, Branda EM, Kruschel CK (1999) The effects of atypical antipsychotics and phencyclidine (PCP) on rotorod performance. Pharmacol Biochem Behav 63:387-394
51. Swanson CJ, Bures M, Johnson MP, Linden AM, Monn JA, Schoepp DD (2005) Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat Rev Drug Discov 4:131-144
52. Takamori K, Hirota S, Chaki S, Tanaka M (2003) Antipsychotic action of selective group II metabotropic glutamate receptor agonist MGS0008 and MGS0028 on conditioned avoidance responses in the rat. Life Sci 73:1721-1728
53. Vandergriff J, Rasmussen K (1999) The selective mGlu2/3 receptor agonist LY354740 attenuates morphine-withdrawal-induced activation of locus coeruleus neurons and behavioral signs of morphine withdrawal. Neuropharmacology 38:217-222
54. Wadenberg ML, Soliman A, VanderSpek SC, Kapur S (2001) Dopamine D(2) receptor occupancy is a common mechanism underlying animal models of antipsychotics and their clinical effects. Neuropsychopharmacology 25:633-641