TABLE 2

Selectivity profile of basimglurant

Data generated at a single concentration of 10 μM (CEREP, DiscoverX) represent the mean of N = 2, K_i 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 K_i or IC₅₀ (for dose response measurements).

	Activity
	% Control	K_i
		µM
Radioligand binding assays
Receptors: low-molecular-weight ligands
Adenosine A₁ receptor (h)^{^a}	12
Adenosine A_2A receptor (h)^{^a}	7
Adenosine A₃ receptor (h)^{^a}	28
Adrenergic α₁ receptor (N.S.) (r)^{^a}	41
Adrenergic α₂ receptor (nonselective) ( r)^{^a}	5
Adrenergic β₁ receptor (h)^{^a}	14
Adrenergic β₂ receptor (h)^{^a}	N.A.D.
Cannabinoid receptor 1 (h)^{^a}^,^{^b}		>8.8
Cannabinoid receptor 2 (h)^{^a}^,^{^b}		2.9
Dopamine D₁ receptor (h)^{^a}	14
Dopamine D₂ receptor (h)^{^a}	N.A.D.
Dopamine D₃ receptor (h)^{^a}	9
Dopamine D₄ receptor (D4.4 variant) (h)^{^a}	10
Histamine H₁ receptor (h)^{^a}	21
Histamine H₂ receptor (h)^{^a}	14
Histamine H₃ receptor (r)^{^a}	11
Melanocortin receptor 4 (h)^{^a}	7
Muscarinic receptors (N.S.) (r)^{^a}	16
Muscarinic receptor 1 (h)^{^a}	12
Muscarinic receptor 2 (h)^{^a}	6
Muscarinic receptor 3 (h)^{^a}	N.A.D.
Muscarinic receptor 4 (h)^{^a}	6
Muscarinic receptor 5 (h)^{^a}	7
Neurokinin receptor 1 (h)^{^a}	24
Neurokinin receptor 2 (h)^{^a}	13
Neurokinin receptor 3 (h)^{^a}	N.A.D.
Opioid receptor (N.S.) (r)^{^a}	2
Purinergic P2X receptor (r)^{^a}	1
Purinergic P2Y receptor (r)^{^a}	8
Serotonin receptor (N.S.) (r)^{^a}	2
Serotonin receptor 5-HT_1A (h)^{^a}	10
Serotonin receptor 5-HT_1B (r)^{^a}	34
Serotonin receptor 5-HT_1D (b)^{^a}	12
Serotonin receptor 5-HT_2A (h)^{^a}	4
Serotonin receptor 5-HT_2B (h)^{^a}	25
Serotonin receptor 5-HT_2C (h)^{^a}	4
Serotonin receptor 5-HT₃ (h)^{^a}	9
Serotonin receptor 5-HT_4c (h)^{^a}	2
Serotonin receptor 5-HT_5a (h)^{^a}	7
Serotonin receptor 5-HT₆ (h)^{^a}	N.A.D.
Serotonin receptor 5-HT₇ (h)^{^a}	23
Sigma receptor (N.S.) (r)^{^a}	7
Sigma receptor 1 (g)^{^a}	6
Sigma receptor 2 (r)^{^a}	22
Receptors: peptides and lipids
Androgen receptor (h)^{^a}	N.A.D.
Angiotensin receptor 1 (h)^{^a}	3
Angiotensin receptor 2 (h)	5
Arginine vasopressin receptor 1a (h)^{^a}	N.A.D.
Arginine vasopressin receptor 2 (h)^{^a}	N.A.D.
Bradykinin receptor B₁ (h)^{^a}	1
Bradykinin receptor B₂ (h)^{^a}	5
Cholecystokinin receptor type A (h)^{^a}	N.A.D.
Cholecystokinin receptor type B (h)^{^a}	4
Corticotropin-releasing factor receptor 1 (r)^{^a}	N.A.D.
Endothelin receptor type A (h)^{^a}	8
Endothelin receptor type B (h)^{^a}	1
Estrogen receptor (nonselective) (h)^{^a}	N.A.D.
Glucocorticoid receptor (h)^{^a}	1
Imidazoline I₁ receptor (b)^{^a}	2
Imidazoline I₂ receptor (r)^{^a}		>6.7
Leukotriene D₄ receptor (CysLT1) (h)^{^a}	2
Neuropeptide Y (nonselective) (r)^{^a}	6
Nociceptin receptor (h)^{^a}	2
Progesterone receptor (h)^{^a}	N.A.D.
Somatostatin receptor (nonselective) (m)^{^a}	N.A.D.
Thyrotropin releasing hormone receptor (r)^{^a}	6
Transporter
Choline transporter (CHT1) (r)^{^a}	N.A.D.
Dopamine transporter (h)^{^a}^,^{^b}	31
GABA transporter (r)^{^a}	11
Norepinephrine transporter (h)^{^a}^,^{^b}	11
Serotonin transporter (h)^{^a}^,^{^b}	24
Ion channels
Acetylcholine rec., nicotinic (α-BGTX insensitive) (r)^{^a}	N.A.D.
AMPA-type glutamate receptor (r)^{^a}	N.A.D.
Ca²⁺ channel, L-type (DHP site) (r)^{^a}	24
Ca²⁺ channel, L-type (diltiazem site) (r)^{^a}	13
Ca²⁺ channel, L-type (verapamil site) (r)^{^a}	2
Ca²⁺ channel, SK type (nonselective) (r)^{^a}	N.A.D.
GABA (N.S.) (r)^{^a}	N.A.D.
GABA_A (central, flunitrazepam) (r)^{^a}	N.A.D.
GABA_A (central, TBPS) (r)^{^a}	N.A.D.
GABA_A (central, flumazenil) (r)^{^c}		>3.2
GABA_A (central, flumazenil; α₅β₃γ₂) (h)^{^c}		>3.2
K⁺ channel, ATP sensitive (K_ir6.2) (r)^{^a}	1
K⁺ channel, voltage gated (α-DTX) (r)^{^a}	N.A.D.
Na⁺ channel (site 2) (r)^{^a}	28
Kainate glutamate receptor (r)^{^a}	7
NMDA glutamate receptor (r)^{^a}	N.A.D.
Functional assays (% control, IC₅₀ [µM])
Acetylcholinesterase (h)^{^a}	8
Adenylate cyclase (r)^{^a}	3
Cannabinoid receptor 1 (h)^{^a}^,^{^b}^,^{^d}		>10
Cannabinoid receptor 2 (h)^{^a}^,^{^b}^,^{^e}		1.7
Catechol-O-methyl transferase (p)^{^a}	19
Dopamine reuptake transporter (h)^{^b}^,^{^c}		>10
GABA transaminase (r)^{^a}	1
Guanylate cyclase (b)^{^a}	1
Metabotropic glutamate receptor 1^{^c}		>10
Metabotropic glutamate receptor 2^{^c}		>10
Metabotropic glutamate receptor 3^{^f}		>10
Metabotropic glutamate receptor 4^{^c}		>10
Metabotropic glutamate receptor 6^{^f}		>10
Metabotropic glutamate receptor 7^{^c}		>10
Metabotropic glutamate receptor 8^{^c}		>10
Monoaminoxidase A (h)^{^a}	1
Monoaminoxidase B (h)^{^a}	12
Na⁺/K⁺-ATPase (d)^{^a}	2
Norepinephrine reuptake transporter (h)^{^c}		>10
Phenylethanolamine N-methyl transferase (h)^{^a}	2
Phosphodiesterase 1 (b)^{^a}	8
Phosphodiesterase 2 (h)^{^a}	3
Phosphodiesterase 3 (h)^{^a}	6
Phosphodiesterase 4 (h)^{^a}	8
Phosphodiesterase 5 (h)^{^a}	N.A.D.
Protein kinase C (r)^{^a}	29
Serotonin reuptake transporter (h)^{^b}^,^{^c}		>10
Tyrosine hydroxylase (r)^{^a}	5

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.