TABLE 2

Pharmacology of commercially available mGlu1 allosteric ligands

For a complete list refer to guidetopharmacology.org.

CompoundIUPAC nameMechanism of ActionSelectivitya (pKB or pEC50/pIC50)In vivo activityRefb
A-8417203-(azepan-1-yl)-9-(dimethylamino)pyrido[1,2] thieno[3,4-d]pyrimidin-4-oneNAMrR1: 9.0; hR1: 8.0; rR5: 6.7Analgesic; disrupts locomotion and cognition1
BAY-36-7620[(3aS,6aS)- 6a-naphtalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental[c]furan-1-on]NAMrR1: 8.0; hR1: <5Anticonvulsive, cognitive impairments2
CFMTI2-cyclopropyl-5-[1-(2-fluoropyridin-3-yl)-5-methyltriazol-4-yl]-3H-isoindol-1-oneNAMhR1: 8.6; rR1: 8.6; hR5: 5.3Antipsychotic-like; no motor effects3
CPCCOEtethyl (7Z)-7-hydroxyimino-1,7a-dihydrocyclopropa[b]chromene-1a-carboxylateNAMrR1: 5.3-4.9; hR1: 4.8; rR5: 4.9; hR5: 4.4; R4: <4Antitumorigenic (melanoma), analgesia, memory impairment, reverses morphine tolerance; neuroprotective (trauma)4
DFMTI (MK-5435)5-(1-(2,4-difluorophenyl)-5-methyl-1H-1,2,3-triazol-4-yl)-2-isopropylisoindolin-1-oneNAMrR1: 8.4-8.1; hR1: 8.4-7.5; hR5: 5.85
DM-PPP4-O-[(2S)-3,3-dimethylbutan-2-yl] 2-O-propyl 3,5-dimethyl-1H-pyrrole-2,4-dicarboxylateNAMrR1: 7.8Analgesic6
EM-TBPC1-ethyl-2-methyl-6-oxo-4-(1,2,4,5-tetrahydro-3-benzazepin-3-yl)pyrimidine-5-carbonitrileNAMrR1: 8.2; hR1: lowNot suitable for in vivo dosing7
FITM, [18F]FITM4-fluoro-N-methyl-N-[4-[6-(propan-2-ylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]benzamideNAMhR1: 6.6; rR1: 8.7; R5: 5.28
FPTQ6-(1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl)quinolineNAMhR1: 7.99
FTIDC4-[1-(2-fluoropyridin-3-yl)-5-methyltriazol-4-yl]-N-methyl-N-propan-2-yl-3,6-dihydro-2H-pyridine-1-carboxamideNAM inverse agonisthR1: 8.2-8; mR1: 8.5; hR5: 5.2; rR5: 510
JNJ162596853,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl-(4-methoxycyclohexyl)methanoneNAM inverse agonisthR1: 7.7-8.9; rR1: 8.3; hR5: 5.8-4.5Antipsychotic-like, antiabuse/addiction, anxiolytic, cognitive impairment, no tolerance with repeat dosing, protective in retinal neurodegeneration11
LY4560662-[[4-(2,3-dihydro-1H-inden-2-ylamino)-5,6,7,8-tetrahydroquinazolin-2-yl]sulfanyl]ethanolNAMhR1: 7.7; hR5: <512
LY4562366-methoxy-N-(4-methoxyphenyl)quinazolin-4-amine hydrochlorideNAMrR1: 5.9; hR1: 6.9-5.5Analgesic, anticonvulsant13
R214127, [3H]R2141271-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenylethanoneNAMrR1:8.9-8.6; hR1: 7.514
RO 67-74762-(4-fluorophenyl)-1-(4-methylphenyl)sulfonylpyrrolidinePAMrR1: 6.8-6.7; hR1: <515
RO 01-6128ethyl N-[2,2-di(phenyl)acetyl]carbamatePAMrR1: 6.7-6.6; hR1: <515
VU04836053-chloro-N-[3-chloro-4-(4-chloro-1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)phenyl]-2-pyridinecarboxamidePAMhR1: 6.4; rR1: 6.0; hR4: <5; rR5(NAL): 6.516
YM2981986-amino-N-cyclohexyl-N,3-dimethylthiazolo[3,2-a]benzimidazole-2-carboxamideNAMhR1: 6.9; rR1: 7.7; hR5: <5.2Antipsychotic-like; analgesic, no motor impairments17
  • IUPAC, International Union of Pure and Applied Chemistry; MoA, mechanism of action; pKB, negative logarithm of the equilbrium dissociation constant for an allosteric ligand; pEC50, negative logarithm of the agonist or PAM concentration required to give the half-maximal response (activation or potentiation); pIC50, negative logarithm of the NAM concentration required to give the half-maximal inhibition.

  • a Where affinity estimates were unavailable pIC50 (NAMs) or pEC50 (PAMs) values are reported indicated by italics.

  • b 1) Zheng et al., 2005; El-Kouhen et al., 2006; Morè et al., 2007; Zhu et al., 2008. 2) Carroll et al., 2001; De Vry et al., 2001; Lavreysen et al., 2003; Schröder et al., 2008; Cho et al., 2014a. 3) Suzuki et al., 2007a, 2010; Satow et al., 2009; Hikichi et al., 2010a. 4) Annoura et al., 1996; Hermans et al., 1998; Litschig et al., 1999; Bhave et al., 2001; Faden et al., 2001; Lavreysen et al., 2003; Marino et al., 2003b; Smith et al., 2004; Kohara et al., 2005; Fukunaga et al., 2007; Haas et al., 2007; Kim et al., 2007; Ansah et al., 2009; Kumar et al., 2010; Song et al., 2012; Gelb et al., 2015a; Hellyer et al., 2018. 5) Ito et al., 2009; Cho et al., 2014a. 6) Micheli et al., 2003. 7) Malherbe et al., 2003. 8) Yamasaki et al., 2012; Cho et al., 2014a; Wu et al., 2014. 9) Suzuki et al., 2009; Fujinaga et al., 2011. 10) Suzuki et al., 2007a; Fukuda et al., 2009; Satow et al., 2009. 11) Lavreysen et al., 2004; Fukunaga et al., 2007; Fukuda et al., 2009; Hikichi et al., 2010b; Scandroglio et al., 2010; Achat-Mendes et al., 2012; Cho et al., 2014a; Steckler et al., 2005a,b; Liberatore et al., 2017. 12) Fukuda et al., 2009; Suzuki et al., 2009. 13) Barton et al., 2003; Shannon et al., 2005; Varty et al., 2005; Cho et al., 2014a. 14) Lavreysen et al., 2003; Chen et al., 2008; Sheffler and Conn, 2008; Suzuki et al., 2009. 15) Knoflach et al., 2001; Sheffler and Conn, 2008. 16) Cho et al., 2014b; Hellyer et al., 2018. 17) Kohara et al., 2005; Fukuda et al., 2009; Suzuki et al., 2009; Hikichi et al., 2010b; Scandroglio et al., 2010.