Metabotropic Glutamate Receptor Data

Receptor Subtype Group I Group II Group III PLD Coupled mGlu Receptor
Subtypes mGlu1
mGlu5
mGlu2
mGlu3
mGlu4
mGlu6
mGlu7
mGlu8
Undetermined
Transduction Mechanism ↑ PLC ↓ AC ↓ AC ↑ PLD
Example Agonists L-Quisqualic acid (0188)
(S)-3,5-DHPG (0805)
CHPG (1049)
DCG-IV (0975)
L-CCG-I (0333)
(2R,4S)-APDC (1208)
LY 379268 (2453)
LY 354740 (3246)
L-AP4 (0103)
(S-3,4-DCPG (1302)
ACPT I (1111)
(RS)-PPG (1220)
VU 0155041 (3248)
L-CSA (0216)
Example Antagonists CPCCOEt (1028)
AIDA (0904)
Fenobam (2386)
MPEP (1212)
LY 367385 (1237)
YM 298198 (2448)
(RS)-APICA (1073)
EGLU (0971)
LY 341495 (1209)
CPPG (0972)
MAP4 (0711)
MSOP (0803)
UBP 1112 (1369)
MMPIP (2963)
(RS)-3,5-DHPG (0342)

Properties of Selected Metabotropic Glutamate Receptor Antagonists

Group I

Antagonist mGlu1a mGlu5a mGlu2 mGlu3 mGlu4 mGlu6 mGlu7 mGlu8
(S)-MCPG (0337) 124-543 (Kb) 154-460 (Kb)
> 2000 (Kb)
15 (Ki) 317 (Ki) > 1000 (IC50) > 100 (IC50) > 1000 (IC50) 320 (IC50)
(S)-4CPG (0323) 15-182 (Kb) > 1000 (Kb)
145 (Kb)
> 300 (Kb)
366 (Ki)
Weak agonist
ND > 1000 (IC50) Weak agonist ND Agonist
(S)-4C3HPG (0320) 11.5-393 (Kb) 157 (Kb)
Agonist ND > 1000 (IC50) ND ND Agonist
AIDA (0904) 3.4 (pKb) > 1000 (IC50) Weak agonist ND > 1000 (IC50) ND ND ND
CPCCOEt (1028) 4.76 (pKb) > 100 (IC50) > 100 (IC50) ND > 100 (IC50) ND > 100 (IC50) > 100 (IC50)
MPEP (1212) > 100 (IC50) 0.032 (IC50) > 100 (IC50) ND > 100 (IC50) > 100 (IC50) > 100 (IC50) ND
SIB 1757 (1215) > 1000 (IC50) 0.4 (IC50 > 30 (IC50) ND > 30 (IC50) > 30 (IC50) > 30 (IC50) > 30 (IC50)
SIB 1893 (1214) > 30 (IC50) 0.3 (IC50) > 30 (IC50) ND > 30 (IC50) > 30 (IC50) > 30 (IC50) > 30 (IC50)
LY 367385 (1237) 8.8 (IC50) > 100 (IC50) ND ND ND ND ND ND
3-MATIDA (2196) 6.3 (IC50) > 300 (IC50) > 300 (IC50) ND > 300 (IC50) ND ND ND

Group II and III

Antagonist mGlu1a mGlu5a mGlu2 mGlu3 mGlu4 mGlu6 mGlu7 mGlu8
MPPG (0853) 1100 (IC50) No effect 12 (Ki) ND 22 (KD) 138 (Kb) ND 20 (IC50)
MAP4 (0711) No effect ND 15 (Ki)
Weak agonist
ND 36 (KD)
190 (Ki)
Weak moderate agonist ND 25 (IC50)
DCG IV (0975) 389 (IC50) 630 (IC50)
Agonist Agonist 22.5 (IC50) 39.6 (IC50) 40.1 (IC50) 32 (IC50)
ACPT-II (1112) 115 (Kb) ND 88 (Kb) ND 77 (Kb) ND ND 123 (IC50)
LY 341495 (1209) 6.8 (IC50) 8.2 (IC50) 0.002 (Ki) 0.001 (Ki) 22 (IC50) ND 0.99 (IC50) 0.173 (IC50)

References

Doherty et al (1999) Br.J.Pharmacol. 126 205. Lin et al (1997) Neuropharmacology 36 917. Brabet et al (1995) Neuropharmacology 34 895. Cartmell et al (1998) Br.J.Pharmacol. 123 497. Laurie et al (1995) Naunyn-Schmied.Arch.Pharmacol. 351 565. Hayashi et al (1994) J.Neurosci. 14 3370. Laurie et al (1997) Neuropharmacology 36 145. Saugstad et al (1994) Mol.Pharmacol. 45 367. Saugstad et al (1997) Mol.Pharmacol. 51 119. Thomsen et al (1994) Eur.J.Pharmacol.Mol.Pharmacol.Sect. 267 77. De Colle et al (2000) Eur.J.Pharmacol. 394 17. Kingston et al (1995) Neuropharmacology 34 887. Bräuner-Osborne et al (1998) Eur.J.Pharmacol. 350 311. Hermans et al (1999) Br.J.Pharmacol. 126 873. Moroni et al (1997) J.Pharmacol.Exp.Ther. 281 721. Hermans et al (1998) Neuropharmacology 37 1645. Litschig et al (1999) Mol.Pharmacol. 55 453. Gasparini et al (1999) Neuropharmacology 38 1493. Varney et al (1999) J.Pharmacol.Exp.Ther. 290 170. Thomsen et al (1996) Mol.Pharmacol. 50 6. Kowal et al (1998) Soc.Neurosci.Abstr. 24 576. Abe et al (1992) J.Biol.Chem. 267 13361. Sekiyama et al (1996) Br.J.Pharmacol. 117 1493. Brabet et al (1998) Neuropharmacology 37 1043. Acher et al (1997) J.Med.Chem. 40 3119. Clark et al (1997) Bioorg.Med.Chem. 7 2777. Johnson et al (1999) Neuropharmacology 38 1519. Moroni et al (2002) Neuropharmacology 42 741.