The antinociceptive and anxiolytic-like effects of the metabotropic glutamate receptor 5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist, LY456236, in rodents: A comparison of efficacy and side-effect profiles

Psychopharmacology

Volumn 179, Issue 1, 2005, Pages 207-217

  Varty, Geoffrey B ^a   Grilli, Mariagrazia ^b   Forlani, Angelo ^b   Fredduzzi, Silva ^b   Grzelak, Michael E ^a   Guthrie, Donald H ^a   Hodgson, Robert A ^a   Lu, Sherry X ^a   Nicolussi, Elisa ^b   Pond, Annamarie J ^a   Parker, Eric M ^a   Hunter, John C ^a   Higgins, Guy A ^a   Reggiani, Angelo ^b   Bertorelli, Rosalia ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b Schering Plough Research Institute   (Italy)

Author keywords

Anxiolysis; Behavior; mGluR1; mGluR5; Neuropathic pain

Indexed keywords

(4 METHOXYPHENYL)(6 METHOXYQUINAZOLIN 4 YL)AMINE; 2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; 3 [(2 METHYL 4 THIAZOLYL)ETHYNYL]PYRIDINE; BENZODIAZEPINE; CHLORDIAZEPOXIDE; FORMALDEHYDE; LY 456236; METABOTROPIC RECEPTOR 1; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR 5 ANTAGONIST; METABOTROPIC RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ALLODYNIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINOCICEPTION; ANXIETY; ARTICLE; BODY TEMPERATURE; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFECT; DRUG EFFICACY; HYPERALGESIA; HYPOTHERMIA; INSTRUMENTAL CONDITIONING; LICKING; LOCOMOTION; MALE; MOUSE; NERVE LIGATION; NONHUMAN; PAIN; PRIORITY JOURNAL; RAT; ROTAROD TEST; SPINAL NERVE; TRANQUILIZING ACTIVITY;

ANALGESICS; ANIMALS; ANTI-ANXIETY AGENTS; BODY TEMPERATURE; CONDITIONING (PSYCHOLOGY); EXCITATORY AMINO ACID ANTAGONISTS; MALE; MICE; MOTOR ACTIVITY; PYRIDINES; QUINAZOLINES; RATS; RECEPTORS, METABOTROPIC GLUTAMATE; THIAZOLES;

EID: 20944438126     PISSN: 00333158     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00213-005-2143-4     Document Type: Article

References (52)

1. 3H]Methoxymethyl-3-[(2- methyl-1,3-thiazol-4-yl)ethynyl]-pyridine binding to metabotropic glutamate receptor subtype 5 in rodent brain: in vitro and in vivo characterization. J Pharmacol Exp Ther 303:1044-1051
2. 3H]3-methoxy-5- (pyridin-2-ylethynyl)pyridine). Eur J Pharmacol 473:35-40
3. Barton ME, Peters SC, Shannon HE (2003) Comparison of the effect of glutamate receptor modulators in the 6 Hz and maximal electroshock seizure models. Epilepsy Res 56:17-26
4. Bhave G, Karim F, Carlton SM, Gereau RW IV (2001) Peripheral group I metabotropic glutamate receptors modulate nociception in mice. Nat Neurosci 4:417-423
5. Bordi F, Ugolini A (1999) Group I metabotropic glutamate receptors: implications for brain diseases. Prog Neurobiol 59:55-79
6. Bordi F, Ugolini A (2000) Involvement of mGluR(5) on acute nociceptive transmission. Brain Res 871:223-233
7. Brodkin J, Busse C, Sukoff SJ, Varney MA (2002a) Anxiolytic-like activity of the mGluR5 antagonist MPEP a comparison with diazepam and buspirone. Pharmacol Biochem Behav 73:359-366
8. Brodkin J, Bradbury M, Busse C, Warren N, Bristow LJ, Varney MA (2002b) Reduced stress-induced hyperthermia in mGluR5 knockout mice. Eur J Neurosci 16:2241-2244
9. Brody SA, Conquet F, Geyer MA (2003) Disruption of prepulse inhibition in mice lacking mGluR1. Eur J Neurosci 18:3361-3366
10. Brody SA, Dulawa SC, Conquet F, Geyer MA (2004) Assessment of a prepulse inhibition deficit in a mutant mouse lacking mGlu5 receptors. Mol Psychiatry 9:35-41
11. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55-63
12. Conn PJ, Pin JP (1997) Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 37:205-237
13. Cosford NDP, Tehrani L, Roppe J, Schweiger E, Smith ND, Anderson J, Bristol L, Brodkin J, Jiang X, McDonald I, Rao S, Washburn M, Varney MA (2003) 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity. J Med Chem 46:204-206
14. Dogrul A, Ossipov MH, Lai J, Malan TP Jr, Porreca F (2000) Peripheral and spinal antihyperalgesic activity of SIB-1757, a metabotropic glutamate receptor (mGLUR(5)) antagonist, in experimental neuropathic pain in rats. Neurosci Lett 292:115-118
15. Dolan S, Nolan AM (2002) Behavioral evidence supporting a differential role for spinal group I and II metabotropic glutamate receptors in inflammatory hyperalgesia in sheep. Neuropharmacology 43:319-326
16. Dolan S, Kelly JG, Monteiro AM, Nolan AM (2003) Up-regulation of metabotropic glutamate receptor subtypes 3 and 5 in spinal cord in a clinical model of persistent inflammation and hyperalgesia. Pain 106:501-512
17. Fisher K, Coderre TJ (1998) Hyperalgesia and allodynia induced by intrathecal (RS)-dihydroxyphenylglycine in rats. NeuroReport 20:1169-1172
18. Fisher K, Lefebvre C, Coderre TJ (2002) Antinociceptive effects following intrathecal pretreatment with selective metabotropic glutamate receptor compounds in a rat model of neuropathic pain. Pharmacol Biochem Behav 73:411-418
19. Fundytus ME, Fisher K, Dray A, Henry JL, Coderre TJ (1998) In vivo antinociceptive activity of anti-rat mGluR1 and mGluR5 antibodies in rats. NeuroReport 9:731-735
20. Fundytus ME, Yashpal K, Chabot JG, Osborne MG, Lefebvre CD, Dray A, Henry JL, Coderre TJ (2001) Knockdown of spinal metabotropic glutamate receptor 1 (mGluR(1)) alleviates pain and restores opioid efficacy after nerve injury in rats. Br J Pharmacol 132:354-367
21. Fundytus ME, Osborne MG, Henry JL, Coderre TJ, Dray A (2002) Antisense oligonucleotide knockdown of mGluR1 alleviates hyperalgesia and allodynia associated with chronic inflammation. Pharmacol Biochem Behav 73:401-410
22. Gasparini F, Lingenhohl K, Stoehr N, Flor PJ, Heinrich M, Vranesic I, Biollaz M, Allgeier H, Heckendorn R, Urwyler S, Varney MA, Johnson EC, Hess SD, Rao SP, Sacaan AI, Santori EM, Velicelebi G, Kuhn R (1999) 2-Methyl-6- (phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 38:1493-1503
23. Hofmann HA, Siegling A, Denzer D, Spreyer P, De Vry J (2001) Metabotropic glutamate mGlu1 receptor mRNA expression in dorsal root ganglia of rats after peripheral nerve injury. Eur J Pharmacol 429:135-138
24. Hudson LJ, Bevan S, McNair K, Gentry C, Fox A, Kuhn R, Winter J (2002) Metabotropic glutamate receptor 5 upregulation in A-fibers after spinal nerve injury: 2-methyl-6-(phenylethynyl)-pyridine (MPEP) reverses the induced thermal hyperalgesia. J Neurosci 22:2660-2668
25. Karim F, Wang CC, Gereau RW IV (2001) Metabotropic glutamate receptor subtypes 1 and 5 are activators of extracellular signal-regulated kinase signaling required for inflammatory pain in mice. J Neurosci 21:3771-3779
26. Kim SH, Chung JM (1992) An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50:355-363
27. Kinney GG, Burno M, Campbell UC, Hernandez LM, Rodriguez D, Bristow LJ, Conn PJ (2003) Metabotropic glutamate subtype 5 receptors modulate locomotor activity and sensorimotor gating in rodents. J Pharmacol Exp Ther 306:116-123
28. Klodzinska A, Tatarczynska E, Chojnacka-Wojcik E, Pilc A (2000) Anxiolytic-like effects of group I metabotropic glutamate antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) in rats. Pol J Pharmacol 52:463-466
29. Klodzinska A, Tatarczynska E, Stachowicz K, Chojnacka-Wojcik E (2004a) The anxiolytic-like activity of AIDA (1-aminoindan-1,5-dicarboxylic acid), an mGlu 1 receptor antagonist. J Physiol Pharmacol 55:113-126
30. Klodzinska A, Tatarczynska E, Chojnacka-Wojcik E, Nowak G, Cosford ND, Pilc A (2004b) Anxiolytic-like effects of MTEP, a potent and selective mGlu5 receptor agonist does not involve GABA(A) signaling. Neuropharmacology 47:342-350
31. 3H]R214127: a novel high-affinity radioligand for the mGlul receptor reveals a common binding site shared by multiple allosteric antagonists. Mol Pharmacol 63:1082-1093
32. Li W, Neugebauer V (2004) Differential roles of mGluR1 and mGluR5 in brief and prolonged nociceptive processing in central amygdala neurons. J Neurophysiol 91:13-24
33. Mills CD, Hulsebosch CE (2002) Increased expression of metabotropic glutamate receptor subtype 1 on spinothalamic tract neurons following spinal cord injury in the rat. Neurosci Lett 319:59-62
34. Nakanishi S (1994) Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity. Neuron 13:1031-1037
35. Neugebauer V (2001) Peripheral metabotropic glutamate receptors: fight the pain where it hurts. Trends Neurosci 24:550-552
36. Neugebauer V, Chen PS, Willis WD (1999) Role of metabotropic glutamate receptor subtype mGluR1 in brief nociception and central sensitization of primate STT cells. J Neurophysiol 82:272-282
37. Neugebauer V, Li W, Bird GC, Bhave G, Gereau RW IV (2003) Synaptic plasticity in the amygdala in a model of arthritic pain: differential roles of metabotropic glutamate receptors 1 and 5. J Neurosci 23:52-63
38. Noda K, Anzai T, Ogata M, Akita H, Ogura T, Saji M (2003) Antisense knockdown of spinal-mGluR1 reduces the sustained phase of formalin-induced nociceptive responses. Brain Res 987:194-200
39. Pilc A, Klodzinska A, Branski P, Nowak G, Palucha A, Szewczyk B, Tatarczynska E, Chojnacka-Wojcik E, Wieronska JM (2002) Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats. Neuropharmacology 43:181-187
40. Schoepp DD, Jane DE, Monn JA (1999) Pharmacological agents acting at subtypes of metabotropic glutamate receptors. Neuropharmacology 38:1431-1476
41. Schulz B, Fendt M, Gasparini F, Lingenhohl K, Kuhn R, Koch M (2001) The metabotropic glutamate receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocks fear conditioning in rats. Neuropharmacology 41:1-7
42. Sotgiu ML, Bellomi P, Biella GE (2003) The mGluR5 selective antagonist 6-methyl-2-(phenylethynyl)-pyridine reduces the spinal neuron pain-related activity in mononeuropathic rats. Neurosci Lett 342:85-88
43. Spooren WP, Vassout A, Neijt HC, Kuhn R, Gasparini F, Roux S, Porsolt RD, Gentsch C (2000) Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J Pharmacol Exp Ther 295:1267-1275
44. Tatarczynska E, Klodzinska A, Chojnacka-Wojcik E, Palucha A, Gasparini F, Kuhn R, Pilc A (2001) Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol 132:1423-1430
45. Urban MO, Hama AT, Bradbury M, Anderson J, Varney MA, Bristow L (2003) Role of metabotropic glutamate receptor subtype 5 (mGluR5) in the maintenance of cold hypersensitivity following a peripheral mononeuropathy in the rat. Neuropharmacology 44:983-993
46. Walker K, Bowes M, Panesar M, Davis A, Gentry C, Kesingland A, Gasparini F, Spooren W, Stoehr N, Pagano A, Flor PJ, Vranesic I, Lingenhoehl K, Johnson EC, Varney M, Urban L, Kuhn R (2001a) Metabotropic glutamate receptor subtype 5 (mGlu5) and nociceptive function. I. Selective blockade of mGlu5 receptors in models of acute, persistent and chronic pain. Neuropharmacology 40:1-9
47. Walker K, Reeve A, Bowes M, Winter J, Wotherspoon G, Davis A, Schmid P, Gasparini F, Kuhn R, Urban L (2001b) mGlu5 receptors and nociceptive function. II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia. Neuropharmacology 40:10-19
48. Yashpal K, Fisher K, Chabot JG, Coderre TJ (2001) Differential effects of NMDA and group I mGluR antagonists on both nociception and spinal cord protein kinase C translocation in the formalin test and a model of neuropathic pain in rats. Pain 94:17-29
49. Young MR, Fleetwood-Walker SM, Mitchell R, Munro FE (1994) Evidence for a role of metabotropic glutamate receptors in sustained nociceptive inputs to rat dorsal horn neurons. Neuropharmacology 33:141-144
50. Young MR, Fleetwood-Walker SM, Dickinson T, Blackburn-Munro G, Sparrow H, Birch PJ, Bountra C (1997) Behavioural and electrophysiological evidence supporting a role for group I metabotropic glutamate receptors in the mediation of nociceptive inputs to the rat spinal cord. Brain Res 777:161-169
51. Young MR, Blackburn-Munro G, Dickinson T, Johnson MJ, Anderson H, Nakalembe I, Fleetwood-Walker SM (1998) Antisense ablation of type I metabotropic glutamate receptor mGluR1 inhibits spinal nociceptive transmission. J Neurosci 18:10180-10188
52. Zhou S, Komak S, Du J, Carlton SM (2001) Metabotropic glutamate 1alpha receptors on peripheral primary afferent fibers: their role in nociception. Brain Res 913:18-26