The M1 muscarinic receptor is thought to be an important therapeutic target in schizophrenia. A cell-based fluorometric calcium assay was developed for high throughput screening. This assay was used to identify compounds with high selectivity for the M1 receptor subtype that act at an allosteric site on the receptor, thus providing increased specificity for this single receptor subtype. It is anticipated that these compounds will provide important tools for the study of muscarinic receptor function in the CNS. ..more
Related BioAssays
Related BioAssays
Target
| Sequence: cholinergic receptor, muscarinic 1 [Homo sapiens] Description ..   Protein Family: Serpentine type 7TM GPCR chemoreceptor Srx Gene:CHRM1 Related Protein 3D Structures |
Tested Compound:
Depositor Specified Assays
| AID | Name | Type | Comment |
|---|---|---|---|
| 626 | Discovery of Novel Allosteric Modulators of the M1 Muscarinic Receptor: Agonist Primary Screen | screening | Discovery of Novel Allosteric Modulators of the M1 Muscarinic Receptor: Agonist Primary Screen |
| 1488 | Discovery of novel allosteric modulators of the M1 muscarinic receptor: Agonist Confirmation Assay | other | Discovery of novel allosteric modulators of the M1 muscarinic receptor: Agonist Confirmation Assay |
| 1798 | Discovery of novel allosteric modulators of the M1 muscarinic receptor: Agonist Probe Summary | summary |
Description:
Assay Provider: P. Jeffrey Conn
Assay Provider Affiliation: Vanderbilt University
Grant Title: Discovery of novel allosteric modulators of the M1 muscarinic receptor
Grant Number: 1 R03 MH077606-01
The M1 muscarinic receptor is thought to be an important therapeutic target in schizophrenia. A cell-based fluorometric calcium assay was developed for high throughput screening. This assay was used to identify compounds with high selectivity for the M1 receptor subtype that act at an allosteric site on the receptor, thus providing increased specificity for this single receptor subtype. It is anticipated that these compounds will provide important tools for the study of muscarinic receptor function in the CNS.
Agents that enhance cholinergic transmission or activate muscarinic acetylcholine receptors (mAChRs) have been developed to ameliorate the loss of cognitive function in patients with Alzheimer's Disease (AD). While cholinergic agents have been partially successful in improving cognitive function in AD patients, the most exciting findings coming from clinical studies with these agents have been the demonstration of efficacy in reducing psychotic symptoms in patients with AD and other neurodegenerative disorders. Interestingly, the M1/M4 preferring mAChR agonist, xanomeline, also induces a robust antipsychotic effect in schizophrenic patients, suggesting that mAChR agonists may have broad utility in reducing psychotic symptoms in patients suffering from schizophrenia and certain neurodegenerative disorders.
Evidence suggests that the antipsychotic effects of cholinergic agents may be mediated by the M1 mAChR subtype. However, previous compounds developed to selectively activate M1 receptors have failed in clinical development due to a lack of true specificity for M1 and adverse effects associated with activation of other mAChR subtypes. Furthermore, the lack of highly selective compounds has made it impossible to definitively determine whether the behavioral and clinical effects of these compounds are mediated by M1 and the M4 receptor subtype is also a viable candidate for mediating the antipsychotic effects.
Previous attempts to develop agonists and antagonists that are highly selective for M1 or other specific mAChR subtypes have failed because of the high conservation of the ACh binding site and difficulty in developing compounds that are truly specific. However, in recent years, major advances have been made in discovery of highly selective antagonists of other G protein-coupled receptors (GPCRs) that act at allosteric sites rather than the orthosteric neurotransmitter binding site [1, 2]. These compounds induce a noncompetitive blockade of receptor function and tend to be highly selective for the targeted receptor. Even more promising for discovery of M1-selective agonists, novel compounds have now been discovered that act at an allosteric site on M1 receptor rather than the orthosteric ACh-binding site to induce a robust activation of the receptor and provide high receptor subtype specificity [3, 4].
1.May, L.T. and A. Christopoulos, Allosteric modulators of G-protein-coupled receptors. Curr Opin Pharmacol, 2003. 3(5): p. 551-6.
2.Gasparini, F., R. Kuhn, and J.P. Pin, Allosteric modulators of group1 metabotropic glutamate receptors: novel subtype-selective ligands and therapeutic perspectives. Curr Opin Pharmacol, 2002. 2(1): p. 43-9.
3.Spalding, T.A., et al., Discovery of an ectopic activation site on the M(1) muscarinic receptor. Mol Pharmacol, 2002. 61(6): p. 1297-302.
4.Sur, C., et al., N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates Nmethyl-D-aspartate receptor activity. Proc Natl Acad Sci USA, 2003. 100(23): p. 13674-9.
Assay Provider Affiliation: Vanderbilt University
Grant Title: Discovery of novel allosteric modulators of the M1 muscarinic receptor
Grant Number: 1 R03 MH077606-01
The M1 muscarinic receptor is thought to be an important therapeutic target in schizophrenia. A cell-based fluorometric calcium assay was developed for high throughput screening. This assay was used to identify compounds with high selectivity for the M1 receptor subtype that act at an allosteric site on the receptor, thus providing increased specificity for this single receptor subtype. It is anticipated that these compounds will provide important tools for the study of muscarinic receptor function in the CNS.
Agents that enhance cholinergic transmission or activate muscarinic acetylcholine receptors (mAChRs) have been developed to ameliorate the loss of cognitive function in patients with Alzheimer's Disease (AD). While cholinergic agents have been partially successful in improving cognitive function in AD patients, the most exciting findings coming from clinical studies with these agents have been the demonstration of efficacy in reducing psychotic symptoms in patients with AD and other neurodegenerative disorders. Interestingly, the M1/M4 preferring mAChR agonist, xanomeline, also induces a robust antipsychotic effect in schizophrenic patients, suggesting that mAChR agonists may have broad utility in reducing psychotic symptoms in patients suffering from schizophrenia and certain neurodegenerative disorders.
Evidence suggests that the antipsychotic effects of cholinergic agents may be mediated by the M1 mAChR subtype. However, previous compounds developed to selectively activate M1 receptors have failed in clinical development due to a lack of true specificity for M1 and adverse effects associated with activation of other mAChR subtypes. Furthermore, the lack of highly selective compounds has made it impossible to definitively determine whether the behavioral and clinical effects of these compounds are mediated by M1 and the M4 receptor subtype is also a viable candidate for mediating the antipsychotic effects.
Previous attempts to develop agonists and antagonists that are highly selective for M1 or other specific mAChR subtypes have failed because of the high conservation of the ACh binding site and difficulty in developing compounds that are truly specific. However, in recent years, major advances have been made in discovery of highly selective antagonists of other G protein-coupled receptors (GPCRs) that act at allosteric sites rather than the orthosteric neurotransmitter binding site [1, 2]. These compounds induce a noncompetitive blockade of receptor function and tend to be highly selective for the targeted receptor. Even more promising for discovery of M1-selective agonists, novel compounds have now been discovered that act at an allosteric site on M1 receptor rather than the orthosteric ACh-binding site to induce a robust activation of the receptor and provide high receptor subtype specificity [3, 4].
1.May, L.T. and A. Christopoulos, Allosteric modulators of G-protein-coupled receptors. Curr Opin Pharmacol, 2003. 3(5): p. 551-6.
2.Gasparini, F., R. Kuhn, and J.P. Pin, Allosteric modulators of group1 metabotropic glutamate receptors: novel subtype-selective ligands and therapeutic perspectives. Curr Opin Pharmacol, 2002. 2(1): p. 43-9.
3.Spalding, T.A., et al., Discovery of an ectopic activation site on the M(1) muscarinic receptor. Mol Pharmacol, 2002. 61(6): p. 1297-302.
4.Sur, C., et al., N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates Nmethyl-D-aspartate receptor activity. Proc Natl Acad Sci USA, 2003. 100(23): p. 13674-9.
Panel Information
M1 muscarinic receptor: Agonist Ancillary Activity
§ Panel component ID.
| Data Table(All) | Show more |
| PID§ | Name | Substance | Panel Targets | Description | Additional Information | ||
|---|---|---|---|---|---|---|---|
| Active | Inactive | ||||||
| 1 | Adenosine A1 (human) | 1 | adenosine A1 receptor [Homo sapiens] [gi:4501947] | Taxonomy id: 9606 Gene id: 134 | |||
| 2 | Adenosine A2 (human) | 1 | adenosine A2a receptor [Homo sapiens] [gi:5921992] | Taxonomy id: 9606 Gene id: 135 | |||
| 3 | Adenosine A3 (human) | 1 | adenosine A3 receptor [Homo sapiens] [gi:4262078] | Taxonomy id: 9606 Gene id: 140 | |||
| 4 | Adrenergic a1A (rat) | 1 | adrenergic, alpha-1A-, receptor [Rattus norvegicus] [gi:148747171] | Taxonomy id: 10116 Gene id: 29412 | |||
| 5 | Adrenergic a1B (rat) | 1 | adrenergic, alpha-1B-, receptor [Rattus norvegicus] [gi:47575853] | Taxonomy id: 10116 Gene id: 24173 | |||
| 6 | Adrenergic a1D (human) | 1 | alpha-1D-adrenergic receptor [Homo sapiens] [gi:4501957] | Taxonomy id: 9606 Gene id: 146 | |||
| 7 | Adrenergic a2A (human) | 1 | alpha-2A-adrenergic receptor [Homo sapiens] [gi:194353970] | Taxonomy id: 9606 Gene id: 150 | |||
| 8 | Adrenergic b1 (human) | 1 | beta-1-adrenergic receptor [Homo sapiens] [gi:4557265] | Taxonomy id: 9606 Gene id: 153 | |||
| 9 | Adrenergic b2 (human) | 1 | adrenergic, beta-2-, receptor, surface [Homo sapiens] [gi:4501969] | Taxonomy id: 9606 Gene id: 154 | |||
| 10 | Androgen (testosterone)AR (rat) | 1 | androgen receptor [Rattus norvegicus] [gi:6978535] | Taxonomy id: 10116 Gene id: 24208 | |||
| 11 | Bradykinin B1 (human) | 1 | bradykinin receptor B1 [Homo sapiens] [gi:20544172] | Taxonomy id: 9606 Gene id: 623 | |||
| 12 | Bradykinin B2 (human) | 1 | bradykinin receptor B2 [Homo sapiens] [gi:4557359] | Taxonomy id: 9606 Gene id: 624 | |||
| 13 | Calcium channel L -type, benzothiazepine (rat) | 1 | Taxonomy id: 10116 | ||||
| 14 | Calcium channel L -type, dihydropyridine (rat) | 1 | calcium channel, voltage-dependent, alpha2/delta subunit 1 isoform 1 [Rattus norvegicus] [gi:31542335] | Taxonomy id: 10116 Gene id: 25399 | |||
| 15 | Calcium channel N-type (rat) | 1 | calcium channel, voltage-dependent, N type, alpha 1B subunit [Rattus norvegicus] [gi:25453410] | Taxonomy id: 10116 Gene id: 257648 | |||
| 16 | Dopamine D 1 (human) | 1 | dopamine receptor D1 [Homo sapiens] [gi:4503383] | Taxonomy id: 9606 Gene id: 1812 | |||
| 17 | Dopamine D 2S (human) | 1 | dopamine receptor D2 isoform short [Homo sapiens] [gi:17986270] | Taxonomy id: 9606 Gene id: 1813 | |||
| 18 | Dopamine D 4.2 (human) | 1 | dopamine receptor D4 [Homo sapiens] [gi:32483397] | Taxonomy id: 9606 Gene id: 1815 | |||
| 19 | Dopamine D3 (human) | 1 | dopamine receptor D3 isoform a [Homo sapiens] [gi:89191861] | Taxonomy id: 9606 Gene id: 1814 | |||
| 20 | Endothelin ETA (human) | 1 | endothelin receptor type A [Homo sapiens] [gi:4503465] | Taxonomy id: 9606 Gene id: 1909 | |||
| 21 | Endothelin ETB (human) | 1 | endothelin receptor type B isoform 1 precursor [Homo sapiens] [gi:4557547] | Taxonomy id: 9606 Gene id: 1910 | |||
| 22 | Epidermal Growth Factor (EGF) (human) | 1 | epidermal growth factor (beta-urogastrone) [Homo sapiens] [gi:166362728] | Taxonomy id: 9606 Gene id: 1950 | |||
| 23 | Estrogen ER a (human) | 1 | estrogen receptor alpha isoform 1 [Homo sapiens] [gi:62821794] | Taxonomy id: 9606 Gene id: 2099 | |||
| 24 | G protein-coupled receptor GPR103 (human) | 1 | G protein-coupled receptor 103 [Homo sapiens] [gi:157738685] | Taxonomy id: 9606 Gene id: 84109 | |||
| 25 | GABA B1A (human) | 1 | gamma-aminobutyric acid (GABA) B receptor 1 isoform a precursor [Homo sapiens] [gi:10835015] | Taxonomy id: 9606 Gene id: 2550 | |||
| 26 | GABAAFlunitrazepam, central (rat) | 1 | Taxonomy id: 10116 | ||||
| 27 | GABAAMuscimol, central (rat) | 1 | gamma-aminobutyric acid (GABA) A receptor, gamma 2 [Rattus norvegicus] [gi:34328527] | Taxonomy id: 10116 Gene id: 29709 | |||
| 28 | Glucocorticoid (human) | 1 | nuclear receptor subfamily 3, group C, member 1 isoform alpha [Homo sapiens] [gi:66528611] | Taxonomy id: 9606 Gene id: 2908 | |||
| 29 | Glutamate, Kainate (rat) | 1 | glutamate receptor, ionotropic, kainate 1 isoform 2 precursor [Rattus norvegicus] [gi:8393481] | Taxonomy id: 10116 Gene id: 29559 | |||
| 30 | Glutamate, NMDA, Agonism (rat) | 1 | glutamate receptor, ionotropic, N-methyl D-aspartate 1 [Rattus norvegicus] [gi:8393484] | Taxonomy id: 10116 Gene id: 24408 | |||
| 31 | Glutamate, NMDA, Glycine (rat) | 1 | glutamate receptor, ionotropic, N-methyl D-aspartate 2B [Rattus norvegicus] [gi:6980984] | Taxonomy id: 10116 Gene id: 24410 | |||
| 32 | Glutamate, NMDA, Phencyclidine (rat) | 1 | glutamate receptor, ionotropic, NMDA2A (epsilon 1) [Mus musculus] [gi:41680705] | Taxonomy id: 10116 Gene id: 14811 | |||
| 33 | Histamine H1 (human) | 1 | histamine receptor H1 [Homo sapiens] [gi:149158709] | Taxonomy id: 9606 Gene id: 3269 | |||
| 34 | Histamine H2 (human) | 1 | histamine receptor H2 isoform 2 [Homo sapiens] [gi:13435405] | Taxonomy id: 9606 Gene id: 3274 | |||
| 35 | Histamine H3 (human) | 1 | histamine receptor H3 [Homo sapiens] [gi:194018562] | Taxonomy id: 9606 Gene id: 11255 | |||
| 36 | Imidazoline I2, central (rat) | 1 | PREDICTED: similar to nischarin [Rattus norvegicus] [gi:109503022] | Taxonomy id: 10116 Gene id: 306255 | |||
| 37 | Interleukin IL-1 (mouse) | 1 | interleukin 1 receptor, type I isoform 1 [Mus musculus] [gi:6680417] | Taxonomy id: 10090 Gene id: 16177 | |||
| 38 | Leukotriene, Cysteinyl CysLT1 (human) | 1 | cysteinyl leukotriene receptor 1 [Homo sapiens] [gi:5729798] | Taxonomy id: 9606 Gene id: 10800 | |||
| 39 | Melatonin MT1 (human) | 1 | melatonin receptor 1A [Homo sapiens] [gi:5174593] | Taxonomy id: 9606 Gene id: 4543 | |||
| 40 | Muscarinic M1 (human) | 1 | cholinergic receptor, muscarinic 1 [Homo sapiens] [gi:37622910] | Taxonomy id: 9606 Gene id: 1128 | |||
| 41 | Muscarinic M2 (human) | 1 | cholinergic receptor, muscarinic 2 [Homo sapiens] [gi:4502817] | Taxonomy id: 9606 Gene id: 1129 | |||
| 42 | Muscarinic M3 (human) | 1 | cholinergic receptor, muscarinic 3 [Homo sapiens] [gi:4502819] | Taxonomy id: 9606 Gene id: 1131 | |||
| 43 | Neuropeptide Y Y1 (human) | 1 | neuropeptide Y receptor Y1 [Homo sapiens] [gi:4505445] | Taxonomy id: 9606 Gene id: 4886 | |||
| 44 | Neuropeptide Y Y2 (human) | 1 | neuropeptide Y receptor Y2 [Homo sapiens] [gi:4505447] | Taxonomy id: 9606 Gene id: 4887 | |||
| 45 | Nicotinic Acetylcholine (human) | 1 | cholinergic receptor, nicotinic, alpha 3 [Homo sapiens] [gi:19923122] | Taxonomy id: 9606 Gene id: 1136 | |||
| 46 | Nicotinic Acetylcholine 1 a , Bungarotoxin (human) | 1 | nicotinic cholinergic receptor alpha 1 isoform b precursor [Homo sapiens] [gi:4557457] | Taxonomy id: 9606 Gene id: 1134 | |||
| 47 | Opiate d (OP1, DOP) (human) | 1 | opioid receptor, delta 1 [Homo sapiens] [gi:63477962] | Taxonomy id: 9606 Gene id: 4985 | |||
| 48 | Opiate k (OP2, KOP) (human) | 1 | opioid receptor, kappa 1 [Homo sapiens] [gi:39725940] | Taxonomy id: 9606 Gene id: 4986 | |||
| 49 | Opiate m (OP3, MOP) (human) | 1 | opioid receptor, mu 1 isoform MOR-1 [Homo sapiens] [gi:117940060] | Taxonomy id: 9606 Gene id: 4988 | |||
| 50 | Phorbol Ester (mouse) | 1 | Taxonomy id: 10090 | ||||
| 51 | Platelet Activating Factor (PAF) (human) | 1 | Taxonomy id: 9606 | ||||
| 52 | Potassium Channel [K ATP] (hamster) | 1 | RecName: Full=G protein-activated inward rectifier potassium channel 2; AltName: Full=GIRK2; AltName: Full=Potassium channel, inwardly rectifying subfamily J member 6; AltName: Full=Inward rectifier K(+) channel Kir3.2; AltName: Full=KATP-2 [gi:1352488] | Taxonomy id: 10036 | |||
| 53 | Potassium Channel hERG (human) | 1 | voltage-gated potassium channel, subfamily H, member 2 isoform a [Homo sapiens] [gi:4557729] | Taxonomy id: 9606 Gene id: 3757 | |||
| 54 | Prostanoid EP4 (human) | 1 | prostaglandin E receptor 4, subtype EP4 [Homo sapiens] [gi:4506259] | Taxonomy id: 9606 Gene id: 5734 | |||
| 55 | Purinergic P2X (rabbit) | 1 | |||||
| 56 | Purinergic P2Y (rat) | 1 | purinergic receptor P2Y, G-protein coupled 1 [Rattus norvegicus] [gi:25742733] | Taxonomy id: 10116 Gene id: 25265 | |||
| 57 | Rolipram (rat) | 1 | Taxonomy id: 10116 | ||||
| 58 | Serotonin (5-Hydroxytryptamine) 5-HT1A (human) | 1 | 5-hydroxytryptamine (serotonin) receptor 1A [Homo sapiens] [gi:55956923] | Taxonomy id: 9606 Gene id: 3350 | |||
| 59 | Serotonin (5-Hydroxytryptamine) 5-HT3 (human) | 1 | 5-hydroxytryptamine (serotonin) receptor 3A isoform b precursor [Homo sapiens] [gi:253735700] | Taxonomy id: 9606 Gene id: 3359 | |||
| 60 | Sigma s1 (human) | 1 | sigma non-opioid intracellular receptor 1 isoform 1 [Homo sapiens] [gi:5032117] | Taxonomy id: 9606 Gene id: 10280 | |||
| 61 | Sigma s2 (rat) | 1 | opioid receptor, sigma 1 [Rattus norvegicus] [gi:13591888] | Taxonomy id: 10116 Gene id: 29336 | |||
| 62 | Sodium Channel, Site 2 (rat) | 1 | sodium channel, voltage-gated, type I, alpha [Rattus norvegicus] [gi:13540709] | Taxonomy id: 10116 Gene id: 81574 | |||
| 63 | Tachykinin NK1 (human) | 1 | tachykinin receptor 1 isoform long [Homo sapiens] [gi:4507343] | Taxonomy id: 9606 Gene id: 6869 | |||
| 64 | Thyroid Hormone (rat) | 1 | c-erbA-alpha2 isoform TRalpha2 [Rattus norvegicus] [gi:63079703] | Taxonomy id: 10116 Gene id: 81812 | |||
| 65 | Transporter, Dopamine (DAT) (human) | 1 | solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 [Homo sapiens] [gi:4507041] | Taxonomy id: 9606 Gene id: 6531 | |||
| 66 | Transporter, GABA (rat) | 1 | vesicular inhibitory amino acid transporter [Rattus norvegicus] [gi:13929106] | Taxonomy id: 10116 Gene id: 83612 | |||
| 67 | Transporter, Norepinephrine (NET) (human) | 1 | solute carrier family 6 member 2 [Homo sapiens] [gi:4557046] | Taxonomy id: 9606 Gene id: 6530 | |||
| 68 | Transporter, Serotonin (5-Hydroxytryptamine) (SERT) (human) | 1 | solute carrier family 6 member 4 [Homo sapiens] [gi:4507043] | Taxonomy id: 9606 Gene id: 6532 | |||
§ Panel component ID.
Protocol
The purpose of this assay was to test the lead compound against a broad panel of targets to determine ancillary activity.
MDS Pharma (The Triad, 2200 Renaissance Blvd, Suite 400, King of Prussia, PA 19406-2755) performed a Lead Profiling Screen of GPCRs, ion channels and transporters against the compound at 10uM concentration. The compond possessed a superior ancillary profile with only three activities >50% at 10 uM, and was thus declared an MLSCN probe.
MDS Pharma (The Triad, 2200 Renaissance Blvd, Suite 400, King of Prussia, PA 19406-2755) performed a Lead Profiling Screen of GPCRs, ion channels and transporters against the compound at 10uM concentration. The compond possessed a superior ancillary profile with only three activities >50% at 10 uM, and was thus declared an MLSCN probe.
Result Definitions
| Show more |
| TID | Name | Description | PID§ | Panel Targets | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||||
| 1 | Activity Outcome | 1 | adenosine A1 receptor [Homo sapiens] |  | Outcome | |||
| 2 | Adenosine A1 (human) (10μM**) | % Inhibition at Adenosine A1 (human) as reported by MDS | 1 | | Integer | % | ||
| 3 | Activity Outcome | 2 | adenosine A2a receptor [Homo sapiens] | | Outcome | |||
| 4 | Adenosine A2 (human) (10μM**) | % Inhibition at Adenosine A2 (human) as reported by MDS | 2 | | Integer | % | ||
| 5 | Activity Outcome | 3 | adenosine A3 receptor [Homo sapiens] | | Outcome | |||
| 6 | Adenosine A3 (human) (10μM**) | % Inhibition at Adenosine A3 (human) as reported by MDS | 3 | | Integer | % | ||
| 7 | Activity Outcome | 4 | adrenergic, alpha-1A-, receptor [Rattus norvegicus] | | Outcome | |||
| 8 | Adrenergic a1A (rat) (10μM**) | % Inhibition at Adrenergic a1A (rat) as reported by MDS | 4 | | Integer | % | ||
| 9 | Activity Outcome | 5 | adrenergic, alpha-1B-, receptor [Rattus norvegicus] | | Outcome | |||
| 10 | Adrenergic a1B (rat) (10μM**) | % Inhibition at Adrenergic a1B (rat) as reported by MDS | 5 | | Integer | % | ||
| 11 | Activity Outcome | 6 | alpha-1D-adrenergic receptor [Homo sapiens] | | Outcome | |||
| 12 | Adrenergic a1D (human) (10μM**) | % Inhibition at Adrenergic a1D (human) as reported by MDS | 6 | | Integer | % | ||
| 13 | Activity Outcome | 7 | alpha-2A-adrenergic receptor [Homo sapiens] | | Outcome | |||
| 14 | Adrenergic a2A (human) (10μM**) | % Inhibition at Adrenergic a2A (human) as reported by MDS | 7 | | Integer | % | ||
| 15 | Activity Outcome | 8 | beta-1-adrenergic receptor [Homo sapiens] | | Outcome | |||
| 16 | Adrenergic b1 (human) (10μM**) | % Inhibition at Adrenergic b1 (human) as reported by MDS | 8 | | Integer | % | ||
| 17 | Activity Outcome | 9 | adrenergic, beta-2-, receptor, surface [Homo sapiens] | | Outcome | |||
| 18 | Adrenergic b2 (human) (10μM**) | % Inhibition at Adrenergic b2 (human) as reported by MDS | 9 | | Integer | % | ||
| 19 | Activity Outcome | 10 | androgen receptor [Rattus norvegicus] | | Outcome | |||
| 20 | Androgen (testosterone)AR (rat) (10μM**) | % Inhibition at Androgen (testosterone)AR (rat) as reported by MDS | 10 | | Integer | % | ||
| 21 | Activity Outcome | 11 | bradykinin receptor B1 [Homo sapiens] | | Outcome | |||
| 22 | Bradykinin B1 (human) (10μM**) | % Inhibition at Bradykinin B1 (human) as reported by MDS | 11 | | Integer | % | ||
| 23 | Activity Outcome | 12 | bradykinin receptor B2 [Homo sapiens] | | Outcome | |||
| 24 | Bradykinin B2 (human) (10μM**) | % Inhibition at Bradykinin B2 (human) as reported by MDS | 12 | | Integer | % | ||
| 25 | Activity Outcome | 13 | | Outcome | ||||
| 26 | Calcium channel L -type, benzothiazepine (rat) (10μM**) | % Inhibition at Calcium channel L -type, benzothiazepine (rat) as reported by MDS | 13 | | Integer | % | ||
| 27 | Activity Outcome | 14 | calcium channel, voltage-dependent, alpha2/delta subunit 1 isoform 1 [Rattus norvegicus] | | Outcome | |||
| 28 | Calcium channel L -type, dihydropyridine (rat) (10μM**) | % Inhibition at Calcium channel L -type, dihydropyridine (rat) as reported by MDS | 14 | | Integer | % | ||
| 29 | Activity Outcome | 15 | calcium channel, voltage-dependent, N type, alpha 1B subunit [Rattus norvegicus] | | Outcome | |||
| 30 | Calcium channel N-type (rat) (10μM**) | % Inhibition at Calcium channel N-type (rat) as reported by MDS | 15 | | Integer | % | ||
| 31 | Activity Outcome | 16 | dopamine receptor D1 [Homo sapiens] | | Outcome | |||
| 32 | Dopamine D 1 (human) (10μM**) | % Inhibition at Dopamine D 1 (human) as reported by MDS | 16 | | Integer | % | ||
| 33 | Activity Outcome | 17 | dopamine receptor D2 isoform short [Homo sapiens] | | Outcome | |||
| 34 | Dopamine D 2S (human) (10μM**) | % Inhibition at Dopamine D 2S (human) as reported by MDS | 17 | | Integer | % | ||
| 35 | Activity Outcome | 18 | dopamine receptor D4 [Homo sapiens] | | Outcome | |||
| 36 | Dopamine D 4.2 (human) (10μM**) | % Inhibition at Dopamine D 4.2 (human) as reported by MDS | 18 | | Integer | % | ||
| 37 | Activity Outcome | 19 | dopamine receptor D3 isoform a [Homo sapiens] | | Outcome | |||
| 38 | Dopamine D3 (human) (10μM**) | % Inhibition at Dopamine D3 (human) as reported by MDS | 19 | | Integer | % | ||
| 39 | Activity Outcome | 20 | endothelin receptor type A [Homo sapiens] | | Outcome | |||
| 40 | Endothelin ETA (human) (10μM**) | % Inhibition at Endothelin ETA (human) as reported by MDS | 20 | | Integer | % | ||
| 41 | Activity Outcome | 21 | endothelin receptor type B isoform 1 precursor [Homo sapiens] | | Outcome | |||
| 42 | Endothelin ETB (human) (10μM**) | % Inhibition at Endothelin ETB (human) as reported by MDS | 21 | | Integer | % | ||
| 43 | Activity Outcome | 22 | epidermal growth factor (beta-urogastrone) [Homo sapiens] | | Outcome | |||
| 44 | Epidermal Growth Factor (EGF) (human) (10μM**) | % Inhibition at Epidermal Growth Factor (EGF) (human) as reported by MDS | 22 | | Integer | % | ||
| 45 | Activity Outcome | 23 | estrogen receptor alpha isoform 1 [Homo sapiens] | | Outcome | |||
| 46 | Estrogen ER a (human) (10μM**) | % Inhibition at Estrogen ER a (human) as reported by MDS | 23 | | Integer | % | ||
| 47 | Activity Outcome | 24 | G protein-coupled receptor 103 [Homo sapiens] | | Outcome | |||
| 48 | G protein-coupled receptor GPR103 (human) (10μM**) | % Inhibition at G protein-coupled receptor GPR103 (human) as reported by MDS | 24 | | Integer | % | ||
| 49 | Activity Outcome | 25 | gamma-aminobutyric acid (GABA) B receptor 1 isoform a precursor [Homo sapiens] | | Outcome | |||
| 50 | GABA B1A (human) (10μM**) | % Inhibition at GABA B1A (human) as reported by MDS | 25 | | Integer | % | ||
| 51 | Activity Outcome | 26 | | Outcome | ||||
| 52 | GABAAFlunitrazepam, central (rat) (10μM**) | % Inhibition at GABAAFlunitrazepam, central (rat) as reported by MDS | 26 | | Integer | % | ||
| 53 | Activity Outcome | 27 | gamma-aminobutyric acid (GABA) A receptor, gamma 2 [Rattus norvegicus] | | Outcome | |||
| 54 | GABAAMuscimol, central (rat) (10μM**) | % Inhibition at GABAAMuscimol, central (rat) as reported by MDS | 27 | | Integer | % | ||
| 55 | Activity Outcome | 28 | nuclear receptor subfamily 3, group C, member 1 isoform alpha [Homo sapiens] | | Outcome | |||
| 56 | Glucocorticoid (human) (10μM**) | % Inhibition at Glucocorticoid (human) as reported by MDS | 28 | | Integer | % | ||
| 57 | Activity Outcome | 29 | glutamate receptor, ionotropic, kainate 1 isoform 2 precursor [Rattus norvegicus] | | Outcome | |||
| 58 | Glutamate, Kainate (rat) (10μM**) | % Inhibition at Glutamate, Kainate (rat) as reported by MDS | 29 | | Integer | % | ||
| 59 | Activity Outcome | 30 | glutamate receptor, ionotropic, N-methyl D-aspartate 1 [Rattus norvegicus] | | Outcome | |||
| 60 | Glutamate, NMDA, Agonism (rat) (10μM**) | % Inhibition at Glutamate, NMDA, Agonism (rat) as reported by MDS | 30 | | Integer | % | ||
| 61 | Activity Outcome | 31 | glutamate receptor, ionotropic, N-methyl D-aspartate 2B [Rattus norvegicus] | | Outcome | |||
| 62 | Glutamate, NMDA, Glycine (rat) (10μM**) | % Inhibition at Glutamate, NMDA, Glycine (rat) as reported by MDS | 31 | | Integer | % | ||
| 63 | Activity Outcome | 32 | glutamate receptor, ionotropic, NMDA2A (epsilon 1) [Mus musculus] | | Outcome | |||
| 64 | Glutamate, NMDA, Phencyclidine (rat) (10μM**) | % Inhibition at Glutamate, NMDA, Phencyclidine (rat) as reported by MDS | 32 | | Integer | % | ||
| 65 | Activity Outcome | 33 | histamine receptor H1 [Homo sapiens] | | Outcome | |||
| 66 | Histamine H1 (human) (10μM**) | % Inhibition at Histamine H1 (human) as reported by MDS | 33 | | Integer | % | ||
| 67 | Activity Outcome | 34 | histamine receptor H2 isoform 2 [Homo sapiens] | | Outcome | |||
| 68 | Histamine H2 (human) (10μM**) | % Inhibition at Histamine H2 (human) as reported by MDS | 34 | | Integer | % | ||
| 69 | Activity Outcome | 35 | histamine receptor H3 [Homo sapiens] | | Outcome | |||
| 70 | Histamine H3 (human) (10μM**) | % Inhibition at Histamine H3 (human) as reported by MDS | 35 | | Integer | % | ||
| 71 | Activity Outcome | 36 | PREDICTED: similar to nischarin [Rattus norvegicus] | | Outcome | |||
| 72 | Imidazoline I2, central (rat) (10μM**) | % Inhibition at Imidazoline I2, central (rat) as reported by MDS | 36 | | Integer | % | ||
| 73 | Activity Outcome | 37 | interleukin 1 receptor, type I isoform 1 [Mus musculus] | | Outcome | |||
| 74 | Interleukin IL-1 (mouse) (10μM**) | % Inhibition at Interleukin IL-1 (mouse) as reported by MDS | 37 | | Integer | % | ||
| 75 | Activity Outcome | 38 | cysteinyl leukotriene receptor 1 [Homo sapiens] | | Outcome | |||
| 76 | Leukotriene, Cysteinyl CysLT1 (human) (10μM**) | % Inhibition at Leukotriene, Cysteinyl CysLT1 (human) as reported by MDS | 38 | | Integer | % | ||
| 77 | Activity Outcome | 39 | melatonin receptor 1A [Homo sapiens] | | Outcome | |||
| 78 | Melatonin MT1 (human) (10μM**) | % Inhibition at Melatonin MT1 (human) as reported by MDS | 39 | | Integer | % | ||
| 79 | Activity Outcome | 40 | cholinergic receptor, muscarinic 1 [Homo sapiens] | | Outcome | |||
| 80 | Muscarinic M1 (human) (10μM**) | % Inhibition at Muscarinic M1 (human) as reported by MDS | 40 | | Integer | % | ||
| 81 | Activity Outcome | 41 | cholinergic receptor, muscarinic 2 [Homo sapiens] | | Outcome | |||
| 82 | Muscarinic M2 (human) (10μM**) | % Inhibition at Muscarinic M2 (human) as reported by MDS | 41 | | Integer | % | ||
| 83 | Activity Outcome | 42 | cholinergic receptor, muscarinic 3 [Homo sapiens] | | Outcome | |||
| 84 | Muscarinic M3 (human) (10μM**) | % Inhibition at Muscarinic M3 (human) as reported by MDS | 42 | | Integer | % | ||
| 85 | Activity Outcome | 43 | neuropeptide Y receptor Y1 [Homo sapiens] | | Outcome | |||
| 86 | Neuropeptide Y Y1 (human) (10μM**) | % Inhibition at Neuropeptide Y Y1 (human) as reported by MDS | 43 | | Integer | % | ||
| 87 | Activity Outcome | 44 | neuropeptide Y receptor Y2 [Homo sapiens] | | Outcome | |||
| 88 | Neuropeptide Y Y2 (human) (10μM**) | % Inhibition at Neuropeptide Y Y2 (human) as reported by MDS | 44 | | Integer | % | ||
| 89 | Activity Outcome | 45 | cholinergic receptor, nicotinic, alpha 3 [Homo sapiens] | | Outcome | |||
| 90 | Nicotinic Acetylcholine (human) (10μM**) | % Inhibition at Nicotinic Acetylcholine (human) as reported by MDS | 45 | | Integer | % | ||
| 91 | Activity Outcome | 46 | nicotinic cholinergic receptor alpha 1 isoform b precursor [Homo sapiens] | | Outcome | |||
| 92 | Nicotinic Acetylcholine 1 a , Bungarotoxin (human) (10μM**) | % Inhibition at Nicotinic Acetylcholine 1 a , Bungarotoxin (human) as reported by MDS | 46 | | Integer | % | ||
| 93 | Activity Outcome | 47 | opioid receptor, delta 1 [Homo sapiens] | | Outcome | |||
| 94 | Opiate d (OP1, DOP) (human) (10μM**) | % Inhibition at Opiate d (OP1, DOP) (human) as reported by MDS | 47 | | Integer | % | ||
| 95 | Activity Outcome | 48 | opioid receptor, kappa 1 [Homo sapiens] | | Outcome | |||
| 96 | Opiate k (OP2, KOP) (human) (10μM**) | % Inhibition at Opiate k (OP2, KOP) (human) as reported by MDS | 48 | | Integer | % | ||
| 97 | Activity Outcome | 49 | opioid receptor, mu 1 isoform MOR-1 [Homo sapiens] | | Outcome | |||
| 98 | Opiate m (OP3, MOP) (human) (10μM**) | % Inhibition at Opiate m (OP3, MOP) (human) as reported by MDS | 49 | | Integer | % | ||
| 99 | Activity Outcome | 50 | | Outcome | ||||
| 100 | Phorbol Ester (mouse) (10μM**) | % Inhibition at Phorbol Ester (mouse) as reported by MDS | 50 | | Integer | % | ||
| 101 | Activity Outcome | 51 | | Outcome | ||||
| 102 | Platelet Activating Factor (PAF) (human) (10μM**) | % Inhibition at Platelet Activating Factor (PAF) (human) as reported by MDS | 51 | | Integer | % | ||
| 103 | Activity Outcome | 52 | RecName: Full=G protein-activated inward rectifier potassium channel 2; AltName: Full=GIRK2; AltName: Full=Potassium channel, inwardly rectifying subfamily J member 6; AltName: Full=Inward rectifier K(+) channel Kir3.2; AltName: Full=KATP-2 | | Outcome | |||
| 104 | Potassium Channel [K ATP] (hamster) (10μM**) | % Inhibition at Potassium Channel [K ATP] (hamster) as reported by MDS | 52 | | Integer | % | ||
| 105 | Activity Outcome | 53 | voltage-gated potassium channel, subfamily H, member 2 isoform a [Homo sapiens] | | Outcome | |||
| 106 | Potassium Channel hERG (human) (10μM**) | % Inhibition at Potassium Channel hERG (human) as reported by MDS | 53 | | Integer | % | ||
| 107 | Activity Outcome | 54 | prostaglandin E receptor 4, subtype EP4 [Homo sapiens] | | Outcome | |||
| 108 | Prostanoid EP4 (human) (10μM**) | % Inhibition at Prostanoid EP4 (human) as reported by MDS | 54 | | Integer | % | ||
| 109 | Activity Outcome | 55 | | Outcome | ||||
| 110 | Purinergic P2X (rabbit) (10μM**) | % Inhibition at Purinergic P2X (rabbit) as reported by MDS | 55 | | Integer | % | ||
| 111 | Activity Outcome | 56 | purinergic receptor P2Y, G-protein coupled 1 [Rattus norvegicus] | | Outcome | |||
| 112 | Purinergic P2Y (rat) (10μM**) | % Inhibition at Purinergic P2Y (rat) as reported by MDS | 56 | | Integer | % | ||
| 113 | Activity Outcome | 57 | | Outcome | ||||
| 114 | Rolipram (rat) (10μM**) | % Inhibition at Rolipram (rat) as reported by MDS | 57 | | Integer | % | ||
| 115 | Activity Outcome | 58 | 5-hydroxytryptamine (serotonin) receptor 1A [Homo sapiens] | | Outcome | |||
| 116 | Serotonin (5-Hydroxytryptamine) 5-HT1A (human) (10μM**) | % Inhibition at Serotonin (5-Hydroxytryptamine) 5-HT1A (human) as reported by MDS | 58 | | Integer | % | ||
| 117 | Activity Outcome | 59 | 5-hydroxytryptamine (serotonin) receptor 3A isoform b precursor [Homo sapiens] | | Outcome | |||
| 118 | Serotonin (5-Hydroxytryptamine) 5-HT3 (human) (10μM**) | % Inhibition at Serotonin (5-Hydroxytryptamine) 5-HT3 (human) as reported by MDS | 59 | | Integer | % | ||
| 119 | Activity Outcome | 60 | sigma non-opioid intracellular receptor 1 isoform 1 [Homo sapiens] | | Outcome | |||
| 120 | Sigma s1 (human) (10μM**) | % Inhibition at Sigma s1 (human) as reported by MDS | 60 | | Integer | % | ||
| 121 | Activity Outcome | 61 | opioid receptor, sigma 1 [Rattus norvegicus] | | Outcome | |||
| 122 | Sigma s2 (rat) (10μM**) | % Inhibition at Sigma s2 (rat) as reported by MDS | 61 | | Integer | % | ||
| 123 | Activity Outcome | 62 | sodium channel, voltage-gated, type I, alpha [Rattus norvegicus] | | Outcome | |||
| 124 | Sodium Channel, Site 2 (rat) (10μM**) | % Inhibition at Sodium Channel, Site 2 (rat) as reported by MDS | 62 | | Integer | % | ||
| 125 | Activity Outcome | 63 | tachykinin receptor 1 isoform long [Homo sapiens] | | Outcome | |||
| 126 | Tachykinin NK1 (human) (10μM**) | % Inhibition at Tachykinin NK1 (human) as reported by MDS | 63 | | Integer | % | ||
| 127 | Activity Outcome | 64 | c-erbA-alpha2 isoform TRalpha2 [Rattus norvegicus] | | Outcome | |||
| 128 | Thyroid Hormone (rat) (10μM**) | % Inhibition at Thyroid Hormone (rat) as reported by MDS | 64 | | Integer | % | ||
| 129 | Activity Outcome | 65 | solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 [Homo sapiens] | | Outcome | |||
| 130 | Transporter, Dopamine (DAT) (human) (10μM**) | % Inhibition at Transporter, Dopamine (DAT) (human) as reported by MDS | 65 | | Integer | % | ||
| 131 | Activity Outcome | 66 | vesicular inhibitory amino acid transporter [Rattus norvegicus] | | Outcome | |||
| 132 | Transporter, GABA (rat) (10μM**) | % Inhibition at Transporter, GABA (rat) as reported by MDS | 66 | | Integer | % | ||
| 133 | Activity Outcome | 67 | solute carrier family 6 member 2 [Homo sapiens] | | Outcome | |||
| 134 | Transporter, Norepinephrine (NET) (human) (10μM**) | % Inhibition at Transporter, Norepinephrine (NET) (human) as reported by MDS | 67 | | Integer | % | ||
| 135 | Activity Outcome | 68 | solute carrier family 6 member 4 [Homo sapiens] | | Outcome | |||
| 136 | Transporter, Serotonin (5-Hydroxytryptamine) (SERT) (human) (10μM**) | % Inhibition at Transporter, Serotonin (5-Hydroxytryptamine) (SERT) (human) as reported by MDS | 68 | | Integer | % |
** Test Concentration. § Panel component ID.
Additional Information
Grant Number: 1 R03 MH077606-01
Classification
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