Selectivity profile of basimglurant

Data generated at a single concentration of 10 μM (CEREP, DiscoverX) represent the mean of N = 2, Ki and IC50 values generated with a concentration range up to 10 μM basimglurant represent the mean of N = 2–6. Values are expressed as % control (for single concentration measurements) or as Ki or IC50 (for dose response measurements).

% ControlKi
Radioligand binding assays
 Receptors: low-molecular-weight ligands
  Adenosine A1 receptor (h)a12
  Adenosine A2A receptor (h)a7
  Adenosine A3 receptor (h)a28
  Adrenergic α1 receptor (N.S.) (r)a41
  Adrenergic α2 receptor (nonselective) ( r)a5
  Adrenergic β1 receptor (h)a14
  Adrenergic β2 receptor (h)aN.A.D.
  Cannabinoid receptor 1 (h)a,b>8.8
  Cannabinoid receptor 2 (h)a,b2.9
  Dopamine D1 receptor (h)a14
  Dopamine D2 receptor (h)aN.A.D.
  Dopamine D3 receptor (h)a9
  Dopamine D4 receptor (D4.4 variant) (h)a10
  Histamine H1 receptor (h)a21
  Histamine H2 receptor (h)a14
  Histamine H3 receptor (r)a11
  Melanocortin receptor 4 (h)a7
  Muscarinic receptors (N.S.) (r)a16
  Muscarinic receptor 1 (h)a12
  Muscarinic receptor 2 (h)a6
  Muscarinic receptor 3 (h)aN.A.D.
  Muscarinic receptor 4 (h)a6
  Muscarinic receptor 5 (h)a7
  Neurokinin receptor 1 (h)a24
  Neurokinin receptor 2 (h)a13
  Neurokinin receptor 3 (h)aN.A.D.
  Opioid receptor (N.S.) (r)a2
  Purinergic P2X receptor (r)a1
  Purinergic P2Y receptor (r)a8
  Serotonin receptor (N.S.) (r)a2
  Serotonin receptor 5-HT1A (h)a10
  Serotonin receptor 5-HT1B (r)a34
  Serotonin receptor 5-HT1D (b)a12
  Serotonin receptor 5-HT2A (h)a4
  Serotonin receptor 5-HT2B (h)a25
  Serotonin receptor 5-HT2C (h)a4
  Serotonin receptor 5-HT3 (h)a9
  Serotonin receptor 5-HT4c (h)a2
  Serotonin receptor 5-HT5a (h)a7
  Serotonin receptor 5-HT6 (h)aN.A.D.
  Serotonin receptor 5-HT7 (h)a23
  Sigma receptor (N.S.) (r)a7
  Sigma receptor 1 (g)a6
  Sigma receptor 2 (r)a22
 Receptors: peptides and lipids
  Androgen receptor (h)aN.A.D.
  Angiotensin receptor 1 (h)a3
  Angiotensin receptor 2 (h)5
  Arginine vasopressin receptor 1a (h)aN.A.D.
  Arginine vasopressin receptor 2 (h)aN.A.D.
  Bradykinin receptor B1 (h)a1
  Bradykinin receptor B2 (h)a5
  Cholecystokinin receptor type A (h)aN.A.D.
  Cholecystokinin receptor type B (h)a4
  Corticotropin-releasing factor receptor 1 (r)aN.A.D.
  Endothelin receptor type A (h)a8
  Endothelin receptor type B (h)a1
  Estrogen receptor (nonselective) (h)aN.A.D.
  Glucocorticoid receptor (h)a1
  Imidazoline I1 receptor (b)a2
  Imidazoline I2 receptor (r)a>6.7
  Leukotriene D4 receptor (CysLT1) (h)a2
  Neuropeptide Y (nonselective) (r)a6
  Nociceptin receptor (h)a2
  Progesterone receptor (h)aN.A.D.
  Somatostatin receptor (nonselective) (m)aN.A.D.
  Thyrotropin releasing hormone receptor (r)a6
  Choline transporter (CHT1) (r)aN.A.D.
  Dopamine transporter (h)a,b31
  GABA transporter (r)a11
  Norepinephrine transporter (h)a,b11
  Serotonin transporter (h)a,b24
 Ion channels
  Acetylcholine rec., nicotinic (α-BGTX insensitive) (r)aN.A.D.
  AMPA-type glutamate receptor (r)aN.A.D.
  Ca2+ channel, L-type (DHP site) (r)a24
  Ca2+ channel, L-type (diltiazem site) (r)a13
  Ca2+ channel, L-type (verapamil site) (r)a2
  Ca2+ channel, SK type (nonselective) (r)aN.A.D.
  GABA (N.S.) (r)aN.A.D.
  GABAA (central, flunitrazepam) (r)aN.A.D.
  GABAA (central, TBPS) (r)aN.A.D.
  GABAA (central, flumazenil) (r)c>3.2
  GABAA (central, flumazenil; α5β3γ2) (h)c>3.2
  K+ channel, ATP sensitive (Kir6.2) (r)a1
  K+ channel, voltage gated (α-DTX) (r)aN.A.D.
  Na+ channel (site 2) (r)a28
  Kainate glutamate receptor (r)a7
  NMDA glutamate receptor (r)aN.A.D.
Functional assays (% control, IC50 [µM])
 Acetylcholinesterase (h)a8
 Adenylate cyclase (r)a3
 Cannabinoid receptor 1 (h)a,b,d>10
 Cannabinoid receptor 2 (h)a,b,e1.7
 Catechol-O-methyl transferase (p)a19
 Dopamine reuptake transporter (h)b,c>10
 GABA transaminase (r)a1
 Guanylate cyclase (b)a1
 Metabotropic glutamate receptor 1c>10
 Metabotropic glutamate receptor 2c>10
 Metabotropic glutamate receptor 3f>10
 Metabotropic glutamate receptor 4c>10
 Metabotropic glutamate receptor 6f>10
 Metabotropic glutamate receptor 7c>10
 Metabotropic glutamate receptor 8c>10
 Monoaminoxidase A (h)a1
 Monoaminoxidase B (h)a12
 Na+/K+-ATPase (d)a2
 Norepinephrine reuptake transporter (h)c>10
 Phenylethanolamine N-methyl transferase (h)a2
 Phosphodiesterase 1 (b)a8
 Phosphodiesterase 2 (h)a3
 Phosphodiesterase 3 (h)a6
 Phosphodiesterase 4 (h)a8
 Phosphodiesterase 5 (h)aN.A.D.
 Protein kinase C (r)a29
 Serotonin reuptake transporter (h)b,c>10
 Tyrosine hydroxylase (r)a5
  • b, bovine; d, dog; g, guinea pig; h, human; m, mouse; N.A.D., no activity detected; NMDA, N-methyl-d-aspartate; N.S., nonselective; p, porcine; r, rat.

  • a Data generated at CEREP.

  • b Targets represented by radioligand binding as well as functional assays.

  • c Data generated at F. Hoffmann-La Roche AG.

  • f Data generated at DiscoverX.

  • d No activity in agonist-, antagonist-, inverse antagonist mode up to 10 µM.

  • e No agonist activity up to 10 µM, inverse agonist activity IC50 = 1.7 µM.