DT-Web

DB04844 - Tetrabenazine


Identification
Name Tetrabenazine
Accession Number DB04844
Type small molecule
Description A drug formerly used as an antipsychotic but now used primarily in the symptomatic treatment of various hyperkinetic disorders. It is a monoamine depletor and used as symptomatic treatment of chorea associated with Huntington's disease. FDA approved on August 15, 2008.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 317.4226
Groups approved
Monoisotopic Weight 317.199093735
Pharmacology
Indication Treatment of hyperkinetic movement disorders like chorea in Huntington's disease, hemiballismus, senile chorea, Tourette syndrome and other tic disorders, and tardive dyskinesia
Mechanism of action Tetrabenazine is a reversible human vesicular monoamine transporter type 2 inhibitor (Ki = 100 nM). It acts within the basal ganglia and promotes depletion of monoamine neurotransmitters serotonin, norepinephrine, and dopamine from stores. It also decreases uptake into synaptic vesicles. Dopamine is required for fine motor movement, so the inhibition of its transmission is efficacious for hyperkinetic movement. Tetrabenazine exhibits weak in vitro binding affinity at the dopamine D2 receptor (Ki = 2100 nM).
Absorption Following oral administration of tetrabenazine, the extent of absorption is at least 75%. After single oral doses ranging from 12.5 to 50 mg, plasma concentrations of tetrabenazine are generally below the limit of detection because of the rapid and extensive hepatic metabolism of tetrabenazine. Food does not affect the absorption of tetrabenazine. Cmax, oral = 4.8 ng/mL in HD or tardive dyskinesia patients; Tmax, oral = 69 min in HD or tardive dyskinesia patients
Protein binding Tetrabenazine = 82 - 88%; ?-HTBZ = 60 - 68%; ?-HTBZ = 59 - 63%.
Biotransformation Tetrabenazine is hepatically metabolized. Carbonyl reductase in the liver is responsible for the formation of two major active metabolites: ?-dihydrotetrabenazine (?-HTBZ) and ?-dihydrotetrabenazine (?-HTBZ). ?-HTBZ is further metabolized into 9-desmethyl-?-DHTBZ, a minor metabolite by CYP2D6 and with some contribution of CYP1A2. ?-HTBZ is metabolized to another major circulating metabolite, 9-desmethyl-?-DHTBZ, by CYP2D6. The Tmax of this metabolite is 2 hours post-administration of tetrabenazine.
Route of elimination After oral administration, tetrabenazine is extensively hepatically metabolized, and the metabolites are primarily renally eliminated (75%). Tetrabenazine is also cleared fecally (7% to 16%). Unchanged tetrabenazine has not been found in human urine. Urinary excretion of ?-HTBZ or ?-HTBZ (the major metabolites) accounted for less than 10% of the administered dose.
Toxicity Dose-limiting adverse effects are sedation, parkinsonism, akathsia, and depression. LD50 oral, mouse: 550 mg/kg
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Acetophenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Aripiprazole May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Chlorpromazine May cause dopamine deficiency. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Clozapine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Cocaine CYP2D6 Inhibitors (Strong) such as cocaine may increase the serum concentration of tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Patients receiving a strong inhibitor of CYP2D6 together with tetrabenazine should not exceed 50mg of tetrabenazine. Also, patients already taking tetrabenazine prior to starting a strong CYP2D6 inhibitor should have their tetrabenazine dose reduced by 50% upon initiation of the strong CYP2D6 inhibitor.
Droperidol May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. May cause dopamine deficiency. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Fluoxetine Strong CYP2D6 inhibitors may increase exposure of the metabolites of tetrabenazine. Consider a reduction of dose.
Flupenthixol May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Fluphenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Furazolidone Tetrabenazine may increase the adverse/toxic effects of Furazolidine. Concomitant therapy is contraindicated.
Haloperidol May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. May cause dopamine deficiency. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Isocarboxazid Tetrabenazine may increase the adverse/toxic effects of Isocarboxazid. Concomitant therapy is contraindicated.
Levodopa Tetrabenazine may cause Parkinsonian symptoms and neutralize the effect of Levodopa.
Linezolid Tetrabenazine may increase the adverse/toxic effects of Linezolid. Concomitant therapy is contraindicated.
Lithium Inhibit biochemical and behavioural effects of tetrabenazine. Heed caution when using agents in combination.
Loxapine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mesoridazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Metoclopramide Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Moclobemide Tetrabenazine may increase the adverse/toxic effects of Moclobemide. Concomitant therapy is contraindicated.
Molindone May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Olanzapine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Paliperidone May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. Similar pharmacologic properties thus combination therapy will worsen the severity of sedative, parkinsonian, and extrapyramidal adverse effects.
Paroxetine Paroxetine is a strong CYP2D6 inhibitor thus increasing half life of dihydrotetrabenazine moieties. Dose of tetrabenazine should be reduced
Perphenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Phenelzine Tetrabenazine may increase the adverse/toxic effects of Phenelzine. Concomitant therapy is contraindicated.
Pimozide May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Procarbazine Tetrabenazine may increase the adverse/toxic effects of Procarbazine. Concomitant therapy is contraindicated.
Prochlorperazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Quetiapine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Quinidine Strong CYP2D6 inhibitors may increase exposure of the metabolites of tetrabenazine. Consider a reduction of dose.
Rasagiline Tetrabenazine may increase the adverse/toxic effects of Rasagiline. Concomitant therapy is contraindicated.
Reserpine Reserpine may increase the adverse/toxic effects of tetrabenazine as they have similar pharmacologic properties. Concomitant therapy is contraindicated.
Risperidone May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Selegiline Tetrabenazine may increase the adverse/toxic effects of Selegiline. Concomitant therapy is contraindicated.
Tacrolimus May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.
Telithromycin Telithromycin may increase the QTc-prolonging effect of Tetrabenazine. Concomitant therapy should be avoided.
Terbinafine Terbinafine may reduce the metabolism and clearance of Tetrabenazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Tetrabenazine if Terbinafine is initiated, discontinued or dose changed.
Thioridazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Thiothixene Additive QTc prolongation may occur. QTc prolongation can lead to Torsade de Pointes (TdP). Concomitant therapy should be avoided.
Toremifene May cause additive QTc-prolonging effects. Concomitant therapy is contraindicated.
Tranylcypromine Tetrabenazine may increase the adverse/toxic effects of Tranylcypromine. Concomitant therapy is contraindicated.
Trifluoperazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Trimipramine May cause additive QTc-prolonging effects. Concomitant therapy should be avoided.
Triprolidine The CNS depressants, Triprolidine and Tetrabenazine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Voriconazole Additive QTc prolongation may occur. Concomitant therapy should be avoided.
Vorinostat Additive QTc prolongation may occur. Concomitant therapy should be avoided.
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Zuclopenthixol Additive QTc prolongation may occur. QTc prolongation can lead to Torsade de Pointes (TdP). Concomitant therapy should be avoided.
Food Interactions Not Available

Targets


Synaptic vesicular amine transporter
Name Synaptic vesicular amine transporter
Gene Name SLC18A2
Pharmacological action yes
Actions inhibitor
References
  • Zheng G, Dwoskin LP, Crooks PA: Vesicular monoamine transporter 2: role as a novel target for drug development. AAPS J. 2006 Nov 10;8(4):E682-92. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Kim YS, Shin JH, Hall FS, Linden DJ: Dopamine signaling is required for depolarization-induced slow current in cerebellar Purkinje cells. J Neurosci. 2009 Jul 1;29(26):8530-8. - Pubmed
  • Goland R, Freeby M, Parsey R, Saisho Y, Kumar D, Simpson N, Hirsch J, Prince M, Maffei A, Mann JJ, Butler PC, Van Heertum R, Leibel RL, Ichise M, Harris PE: 11C-dihydrotetrabenazine PET of the pancreas in subjects with long-standing type 1 diabetes and in healthy controls. J Nucl Med. 2009 Mar;50(3):382-9. Epub 2009 Feb 17. - Pubmed
  • Gros Y, Schuldiner S: Directed evolution reveals hidden properties of VMAT, a neurotransmitter transporter. J Biol Chem. 2010 Feb 12;285(7):5076-84. Epub 2009 Dec 10. - Pubmed
  • Wimalasena K: Vesicular monoamine transporters: Structure-function, pharmacology, and medicinal chemistry. Med Res Rev. 2010 Feb 4. - Pubmed
DTHybrid score 0.5684
D(2) dopamine receptor
Name D(2) dopamine receptor
Gene Name DRD2
Pharmacological action unknown
Actions inhibitor
References
  • FDA label -
DTHybrid score 0.2826

Enzymes


Cytochrome P450 2D6
Name Cytochrome P450 2D6
Gene Name CYP2D6
Actions substrate
References
  • Poon LH, Kang GA, Lee AJ: Role of tetrabenazine for Huntington's disease-associated chorea. Ann Pharmacother. 2010 Jun;44(6):1080-9. Epub 2010 May 4. - Pubmed
DTHybrid score 0.3196
Carbonyl reductase [NADPH] 1
Name Carbonyl reductase [NADPH] 1
Gene Name CBR1
Actions substrate
References
  • Jankovic J, Clarence-Smith K: Tetrabenazine for the treatment of chorea and other hyperkinetic movement disorders. Expert Rev Neurother. 2011 Nov;11(11):1509-23. doi: 10.1586/ern.11.149. - Pubmed
DTHybrid score 0.6593

Predictions


Id Partner name Gene Name Score
5354 DevB protein VC_A0897 0.138
842 Chloride channel protein 2 CLCN2 0.1214
556 Alpha-1A adrenergic receptor ADRA1A 0.1214
4512 Cytochrome P450 3A4 CYP3A4 0.1182
502 5-hydroxytryptamine 2A receptor HTR2A 0.1173
1636 Trace amine-associated receptor 1 TAAR1 0.1056
23 D(1A) dopamine receptor DRD1 0.0959
713 Sodium-dependent dopamine transporter SLC6A3 0.0875
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0778
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0769
1588 Multidrug resistance protein 1 ABCB1 0.0708
4200 Cytochrome P450 1A2 CYP1A2 0.0702
824 Sodium-dependent serotonin transporter SLC6A4 0.067
638 D(3) dopamine receptor DRD3 0.0615
4757 Cytochrome P450 2C9 CYP2C9 0.0606
318 Alpha-2A adrenergic receptor ADRA2A 0.0605
6016 Cytochrome P450 2C19 CYP2C19 0.0578
4118 Cytochrome P450 3A5 CYP3A5 0.0504
590 5-hydroxytryptamine 2C receptor HTR2C 0.0499
320 5-hydroxytryptamine 1A receptor HTR1A 0.0482
6030 Cytochrome P450 2B6 CYP2B6 0.0439
432 D(4) dopamine receptor DRD4 0.0414
632 Alpha-1B adrenergic receptor ADRA1B 0.0411
492 Histamine H1 receptor HRH1 0.041
3941 Amine oxidase [flavin-containing] A MAOA 0.0405
3939 Amine oxidase [flavin-containing] B MAOB 0.0392
629 Alpha-2B adrenergic receptor ADRA2B 0.0388
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0383
6107 Cytochrome P450 3A7 CYP3A7 0.0382
378 Alpha-2C adrenergic receptor ADRA2C 0.0381
4924 Cytochrome P450 2C8 CYP2C8 0.0364
436 5-hydroxytryptamine 2B receptor HTR2B 0.0339
163 D(1B) dopamine receptor DRD5 0.0332
6145 Solute carrier family 22 member 1 SLC22A1 0.0319
6013 Cytochrome P450 2E1 CYP2E1 0.0301
6024 Cytochrome P450 1A1 CYP1A1 0.0264
3923 Cholinesterase BCHE 0.0253
5718 Cytochrome P450 2A6 CYP2A6 0.0245
766 Beta-2 adrenergic receptor ADRB2 0.0243
193 Beta-1 adrenergic receptor ADRB1 0.0233
118 Organic cation/carnitine transporter 2 SLC22A5 0.023
982 Cocaine- and amphetamine-regulated transcript protein CARTPT 0.0219
725 5-hydroxytryptamine 1D receptor HTR1D 0.0212
885 5-hydroxytryptamine 1B receptor HTR1B 0.0211
6144 Solute carrier family 22 member 2 SLC22A2 0.0206
716 5-hydroxytryptamine 7 receptor HTR7 0.0204
474 Acetylcholinesterase ACHE 0.0202
6147 Solute carrier family 22 member 3 SLC22A3 0.0194
4120 NADPH--cytochrome P450 reductase POR 0.0193
617 Muscarinic acetylcholine receptor M2 CHRM2 0.019
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0186
776 Bile salt export pump ABCB11 0.0182
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0171
587 Serum albumin ALB 0.017
465 Calmodulin CALM1 0.0168
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0166
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0166
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0162
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0162
789 Alpha-1D adrenergic receptor ADRA1D 0.0149
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0146
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0134
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0128
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0122
1256 5-hydroxytryptamine 6 receptor HTR6 0.0117
847 Mu-type opioid receptor OPRM1 0.0113
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0112
750 Voltage-dependent calcium channel gamma-1 subunit CACNG1 0.0111
341 5-hydroxytryptamine 3 receptor HTR3A 0.0108
1898 Cytochrome P450 1B1 CYP1B1 0.0101
862 Multidrug resistance-associated protein 1 ABCC1 0.0099
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0097
6172 ATP-binding cassette sub-family B member 8, mitochondrial ABCB8 0.0094
1517 Beta-3 adrenergic receptor ADRB3 0.0094
20 Prostaglandin G/H synthase 1 PTGS1 0.0089
467 Delta-type opioid receptor OPRD1 0.0087
6106 Cytochrome P450 2C18 CYP2C18 0.0085
696 Kappa-type opioid receptor OPRK1 0.0083
3947 Xanthine dehydrogenase/oxidase XDH 0.0083
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0079
817 DNA topoisomerase 2-alpha TOP2A 0.0079
337 NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial NDUFS7 0.0078
214 NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NDUFS3 0.0078
803 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial NDUFS2 0.0078
6861 Alcohol dehydrogenase [NADP+] AKR1A1 0.0078
6168 Solute carrier family 22 member 16 SLC22A16 0.0078
923 Glutamate receptor 3 GRIA3 0.0074
94 5-hydroxytryptamine 4 receptor HTR4 0.0073
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0073
380 Cytochrome P450 17A1 CYP17A1 0.0069
174 Sigma 1-type opioid receptor SIGMAR1 0.0067
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0063
6148 Multidrug resistance-associated protein 7 ABCC10 0.0061
6137 Multidrug resistance-associated protein 6 ABCC6 0.0061
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0061
528 5-hydroxytryptamine 1E receptor HTR1E 0.0059
833 Organic cation/carnitine transporter 1 SLC22A4 0.0057
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0057
76 Nitric-oxide synthase, brain NOS1 0.0057
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0057
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0056
7 Nitric oxide synthase, inducible NOS2 0.0056
291 Nitric-oxide synthase, endothelial NOS3 0.0053
731 HIV-1 protease HIV-1 protease 0.0052
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0051
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.005
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0049
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0049
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0049
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0048
124 Histamine H2 receptor HRH2 0.0047
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0046
921 Glutamate receptor 2 GRIA2 0.0045
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0045
2112 Toll-like receptor 9 TLR9 0.0044
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0043
6859 Protein S100-A4 S100A4 0.0041
1729 Solute carrier family 22 member 6 SLC22A6 0.0041
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.004
694 Matrix protein 2 M 0.0039
360 Ribonucleoside-diphosphate reductase large subunit RRM1 0.0039
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 0.0038
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0038
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0036
4099 Gamma-aminobutyric-acid receptor subunit beta-3 GABRB3 0.0035
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0034
427 Substance-P receptor TACR1 0.0034
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0034
6506 Stathmin-4 STMN4 0.0033
6182 Cytochrome P450 2J2 CYP2J2 0.0033
173 Toll-like receptor 7 TLR7 0.0033
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0033
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0032
4199 Sphingosine 1-phosphate receptor Edg-8 S1PR5 0.0031
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0031
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.003
620 Bifunctional dihydrofolate reductase-thymidylate synthase Not Available 0.003
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0028
565 Extracellular calcium-sensing receptor CASR 0.0028
6031 Cytochrome P450 3A43 CYP3A43 0.0028
1995 Sodium channel protein type 9 subunit alpha SCN9A 0.0027
3804 Sodium channel protein type 4 subunit alpha SCN4A 0.0026
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0025
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.0025
3811 Cytochrome P450 19A1 CYP19A1 0.0025
891 Dihydropteroate synthase folP 0.0025
5359 Dihydropteroate synthase folP 0.0025
7175 Dihydropteroate synthase sulI 0.0025
161 Tubulin beta chain TUBB 0.0024
312 Tubulin beta chain TUB2 0.0024
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0024
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0024
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0024
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0023
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0023
385 Potassium-transporting ATPase alpha chain 1 ATP4A 0.0022
504 Mast/stem cell growth factor receptor KIT 0.0022
6151 Monocarboxylate transporter 10 SLC16A10 0.0021
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0021
952 Dipeptidyl peptidase 4 DPP4 0.0021
63 Malate dehydrogenase mdh 0.0021
2329 Malate dehydrogenase mdh 0.0021
3445 Malate dehydrogenase mdh 0.0021
4420 Malate dehydrogenase mdh 0.0021
4438 Malate dehydrogenase mdh 0.0021
1656 CYP2B protein CYP2B 0.002
365 Dihydrofolate reductase DHFR 0.002
2381 Dihydrofolate reductase DFR1 0.002
2833 Dihydrofolate reductase Not Available 0.002
2931 Dihydrofolate reductase folA 0.002
3544 Dihydrofolate reductase folA 0.002
3682 Dihydrofolate reductase folA 0.002
6642 Dihydrofolate reductase folA 0.002
6756 Dihydrofolate reductase dfrA 0.002
4203 Histamine N-methyltransferase HNMT 0.0019
290 Prostaglandin G/H synthase 2 PTGS2 0.0019
2164 Multidrug resistance-associated protein 4 ABCC4 0.0019
164 Histamine H4 receptor HRH4 0.0019
153 Dopamine beta-hydroxylase DBH 0.0019
871 Glucocorticoid receptor NR3C1 0.0019
200 Carnitine O-palmitoyltransferase 2, mitochondrial CPT2 0.0019
451 Carnitine O-palmitoyltransferase I, liver isoform CPT1A 0.0019
893 [Citrate [pro-3S]-lyase] ligase citC 0.0018
845 Pyruvate dehydrogenase [cytochrome] poxB 0.0018
844 Epidermal growth factor receptor EGFR 0.0018
327 Glutathione reductase gor 0.0018
5110 Glutathione reductase GR2 0.0018
1178 Adenosine A2a receptor ADORA2A 0.0018
748 5'-AMP-activated protein kinase catalytic subunit alpha-1 PRKAA1 0.0018
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0017
4160 Voltage-dependent calcium channel subunit alpha-2/delta-2 CACNA2D2 0.0017
6047 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A PDE1A 0.0016
146 Androgen receptor AR 0.0016
4209 ATP-sensitive inward rectifier potassium channel 8 KCNJ8 0.0016
4228 Keratin, type II cytoskeletal 7 KRT7 0.0016
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0016
6220 Aryl hydrocarbon receptor AHR 0.0016
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.0016
468 Cytochrome P450 4A11 CYP4A11 0.0016
1629 Transcription factor AP-1 JUN 0.0016
5692 Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B PDE1B 0.0016
6180 UDP-glucuronosyltransferase 2B4 UGT2B4 0.0016
6142 Solute carrier family 22 member 8 SLC22A8 0.0016
3810 Catechol O-methyltransferase COMT 0.0015
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0015
4604 Liver carboxylesterase 1 CES1 0.0015
1050 Bile salt sulfotransferase SULT2A1 0.0014
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0014
3086 Plasmepsin-2 Not Available 0.0014
373 Transthyretin TTR 0.0014
485 cGMP-inhibited 3',5'-cyclic phosphodiesterase A PDE3A 0.0014
4148 Serine/threonine-protein kinase mTOR MTOR 0.0014
738 Monocarboxylate transporter 1 SLC16A1 0.0014
208 DNA-directed RNA polymerase beta' chain rpoC 0.0014
5774 DNA-directed RNA polymerase beta' chain rpoC 0.0014
6143 Solute carrier family 22 member 7 SLC22A7 0.0013
698 B-Raf proto-oncogene serine/threonine-protein kinase BRAF 0.0013
3404 Exotoxin A eta 0.0013
17 Proto-oncogene tyrosine-protein kinase ABL1 ABL1 0.0013
950 Alpha platelet-derived growth factor receptor PDGFRA 0.0013
762 Voltage-dependent calcium channel subunit alpha-2/delta-1 CACNA2D1 0.0013
73 Prostaglandin E2 receptor, EP1 subtype PTGER1 0.0013
860 Nicotinamide N-methyltransferase NNMT 0.0013
699 Nicotinic acid receptor 1 GPR109A 0.0013
928 Nicotinic acid receptor 2 GPR109B 0.0013
583 Nicotinate-nucleotide pyrophosphorylase [carboxylating] QPRT 0.0013
2442 Nicotinate-nucleotide pyrophosphorylase [carboxylating] nadC 0.0013
2459 Nicotinate-nucleotide pyrophosphorylase [carboxylating] nadC 0.0013
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0012
1010 Cytochrome P450 51A1 CYP51A1 0.0012
6432 Transporter snf 0.0012
232 Corticosteroid-binding globulin SERPINA6 0.0012
3856 Fibroblast growth factor receptor 3 FGFR3 0.0012
228 Beta platelet-derived growth factor receptor PDGFRB 0.0012
5766 NAD-dependent deacetylase sirtuin-5 SIRT5 0.0012
6102 Arylamine N-acetyltransferase 2 NAT2 0.0012
473 L-lactate dehydrogenase A chain LDHA 0.0011
514 Potassium voltage-gated channel subfamily H member 6 KCNH6 0.0011
772 Potassium voltage-gated channel subfamily H member 7 KCNH7 0.0011
6014 Cytochrome P450 2A13 CYP2A13 0.0011
707 72 kDa type IV collagenase MMP2 0.0011
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0011
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.001
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.001
2290 ADP-ribosyl cyclase 2 BST1 0.001
614 Progesterone receptor PGR 0.001
2300 Lysozyme E 0.001
3633 Lysozyme R 0.001
5597 Lysozyme 17 0.001
407 Vascular endothelial growth factor receptor 2 KDR 0.001
6181 UDP-glucuronosyltransferase 1-8 UGT1A8 0.001
4311 tRNA TRDMT1 0.001
4325 tRNA trmD 0.001
4328 tRNA trmD 0.001
6080 Neuronal acetylcholine receptor subunit alpha-5 CHRNA5 0.001
6082 Neuronal acetylcholine receptor subunit beta-3 CHRNB3 0.001
948 Neuronal acetylcholine receptor subunit beta-2 CHRNB2 0.001
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.001
260 Cytochrome P450 51 ERG11 0.001
761 Cytochrome P450 51 ERG11 0.001
3163 Cytochrome P450 51 cyp51 0.001
144 Hemoglobin subunit alpha HBA1 0.001
518 Peroxidase/catalase T katG 0.001
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.001
777 Tumor necrosis factor TNF 0.0009
6154 Multidrug and toxin extrusion protein 1 SLC47A1 0.0009
6081 Neuronal acetylcholine receptor subunit alpha-6 CHRNA6 0.0009
4097 Neuronal acetylcholine receptor subunit alpha-9 CHRNA9 0.0009
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.0009
3126 Poly [ADP-ribose] polymerase 1 PARP1 0.0009
1064 DNA (cytosine-5)-methyltransferase 1 DNMT1 0.0009
563 Thyroid peroxidase TPO 0.0009
147 Aldehyde dehydrogenase, mitochondrial ALDH2 0.0009
65 Matrix metalloproteinase-9 Not Available 0.0009
26 Vascular endothelial growth factor receptor 3 FLT4 0.0009
295 Carbonic anhydrase 1 CA1 0.0009
741 Potassium voltage-gated channel subfamily KQT member 1 KCNQ1 0.0009
4122 Histone deacetylase 2 HDAC2 0.0009
16 Adenosine A1 receptor ADORA1 0.0009
241 Calcium-transporting ATPase type 2C member 1 ATP2C1 0.0009
32 Vascular endothelial growth factor receptor 1 FLT1 0.0009
634 Squalene monooxygenase SQLE 0.0009
7196 Squalene monooxygenase ERG1 0.0009
204 cGMP-specific 3',5'-cyclic phosphodiesterase PDE5A 0.0009
6078 Neuronal acetylcholine receptor subunit beta-4 CHRNB4 0.0009
1262 Corticotropin-lipotropin POMC 0.0008
1341 Histamine H3 receptor HRH3 0.0008
3932 Glutathione S-transferase A2 GSTA2 0.0008
537 ATP synthase delta chain, mitochondrial ATP5D 0.0008
1192 Sulfotransferase 1A1 SULT1A1 0.0008
778 Cysteinyl leukotriene receptor 1 CYSLTR1 0.0008
522 26S proteasome non-ATPase regulatory subunit 2 PSMD2 0.0008
515 26S proteasome non-ATPase regulatory subunit 1 PSMD1 0.0008
1457 Long-chain-fatty-acid--CoA ligase 4 ACSL4 0.0008
165 FL cytokine receptor FLT3 0.0008
244 Angiotensin-converting enzyme ACE 0.0008
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0008
6126 Carbonic anhydrase 7 CA7 0.0008
6212 Tubulin gamma-1 chain TUBG1 0.0008
6210 Tubulin delta chain TUBD1 0.0008
6211 Tubulin epsilon chain TUBE1 0.0008
2180 3-phosphoinositide-dependent protein kinase 1 PDPK1 0.0008
4177 Proto-oncogene tyrosine-protein kinase receptor ret RET 0.0008
482 Glycine receptor subunit alpha-1 GLRA1 0.0008
500 Monocarboxylate transporter 4 SLC16A3 0.0008
70 Type-1 angiotensin II receptor AGTR1 0.0008
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0008
606 Cytochrome P450 27, mitochondrial CYP27A1 0.0007
541 cAMP-specific 3',5'-cyclic phosphodiesterase 4B PDE4B 0.0007
3854 Basic fibroblast growth factor receptor 1 FGFR1 0.0007
122 P2Y purinoceptor 12 P2RY12 0.0007
6136 Multidrug resistance-associated protein 5 ABCC5 0.0007
581 Cytochrome P450 2R1 CYP2R1 0.0007
580 Gamma-aminobutyric-acid receptor subunit alpha-3 GABRA3 0.0007
423 Gamma-aminobutyric-acid receptor subunit alpha-2 GABRA2 0.0007
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0007
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0007
6038 Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma PDE6H 0.0007
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.0007
4773 Deoxycytidine kinase DCK 0.0007
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0007
1992 Vitamin D-binding protein GC 0.0007
319 Opioid receptor, sigma 1 OPRS1 0.0007
1618 High affinity nerve growth factor receptor NTRK1 0.0007
368 Enoyl-[acyl-carrier-protein] reductase [NADH] inhA 0.0007
3228 Enoyl-[acyl-carrier-protein] reductase [NADH] fabI 0.0007
3678 Enoyl-[acyl-carrier-protein] reductase [NADH] fabI 0.0007
6856 Enoyl-[acyl-carrier-protein] reductase [NADH] fabI 0.0007
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0007
6037 Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma PDE6G 0.0007
737 Mineralocorticoid receptor NR3C2 0.0006
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0006
592 Carbonic anhydrase 4 CA4 0.0006
976 Platelet glycoprotein IX GP9 0.0006
4103 Proteasome subunit beta type 2 PSMB2 0.0006
4102 Proteasome subunit beta type 5 PSMB5 0.0006
4101 Proteasome subunit beta type 1 PSMB1 0.0006
1630 Integrin beta-2 ITGB2 0.0006
1374 Natriuretic peptides B NPPB 0.0006
1827 Gap junction alpha-1 protein GJA1 0.0006
1908 Vascular cell adhesion protein 1 VCAM1 0.0006
2450 Tyrosine-protein kinase ITK/TSK ITK 0.0006
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0006
2216 Fibroblast growth factor receptor 4 FGFR4 0.0006
4095 Neuronal acetylcholine receptor subunit alpha-7 CHRNA7 0.0006
947 Neuronal acetylcholine receptor subunit alpha-4 CHRNA4 0.0006
806 Sodium/potassium-transporting ATPase alpha-1 chain ATP1A1 0.0006
814 Ryanodine receptor 1 RYR1 0.0006
511 5-hydroxytryptamine 1F receptor HTR1F 0.0006
6141 Sodium/bile acid cotransporter SLC10A1 0.0006
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0006
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0006
6146 High affinity copper uptake protein 1 SLC31A1 0.0006
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.0006
1757 Myeloperoxidase MPO 0.0006
2449 Tubulin alpha-3 chain TUBA1A 0.0006
6046 Voltage-gated calcium channel beta 1 subunit splice variant CavB1d CACNB1 0.0006
705 Glutamate receptor 1 GRIA1 0.0006
6048 Troponin C, skeletal muscle TNNC2 0.0005
543 Penicillin-binding protein 1B mrcB 0.0005
6186 Penicillin-binding protein 1B ponB 0.0005
6822 Penicillin-binding protein 1b pbp1b 0.0005
6844 Penicillin-binding protein 1b pbp1b 0.0005
194 NADH dehydrogenase [ubiquinone] 1 subunit C2 NDUFC2 0.0005
645 Penicillin-binding protein 1A mrcA 0.0005
5805 Penicillin-binding protein 1A ponA 0.0005
6185 Penicillin-binding protein 1A mrcA 0.0005
6799 Penicillin-binding protein 1A pbpA 0.0005
268 Adenosine A2b receptor ADORA2B 0.0005
159 Penicillin-binding protein 2B penA 0.0005
6121 Penicillin-binding protein 2B penA 0.0005
6044 Serum paraoxonase/lactonase 3 PON3 0.0005
1024 Solute carrier family 22 member 11 SLC22A11 0.0005
6045 Voltage-dependent calcium channel subunit alpha-2/delta-3 CACNA2D3 0.0005
856 Vitamin D3 receptor VDR 0.0005
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0005
183 Vascular endothelial growth factor A VEGFA 0.0005
572 Integrin alpha-L ITGAL 0.0005
904 Glutathione S-transferase P GSTP1 0.0005
3868 Calcineurin subunit B isoform 2 PPP3R2 0.0005
357 Carbonic anhydrase 2 CA2 0.0005
421 Calcium signal-modulating cyclophilin ligand CAMLG 0.0005
1864 RET proto-oncogene RET 0.0005
1950 Epithelial discoidin domain-containing receptor 1 DDR1 0.0005
6094 BCR/ABL fusion protein isoform X9 BCR/ABL fusion 0.0005
6170 ATP-binding cassette sub-family A member 3 ABCA3 0.0005
233 Potassium channel subfamily K member 2 KCNK2 0.0005
6824 Tyrosine-protein kinase Lyn LYN 0.0005
1275 Estrogen sulfotransferase SULT1E1 0.0004
3802 Sodium channel protein type 2 subunit alpha SCN2A 0.0004
136 Estrogen receptor ESR1 0.0004
760 Fibroblast growth factor 1 FGF1 0.0004
6931 Calcium-activated potassium channel subunit beta-1 KCNMB1 0.0004
6933 Calcium-activated potassium channel subunit beta-4 KCNMB4 0.0004
6932 Calcium-activated potassium channel subunit beta-3 KCNMB3 0.0004
6934 Small conductance calcium-activated potassium channel protein 1 KCNN1 0.0004
6935 Small conductance calcium-activated potassium channel protein 2 KCNN2 0.0004
6936 Small conductance calcium-activated potassium channel protein 3 KCNN3 0.0004
1768 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 subunit GNG2 0.0004
1581 G protein-activated inward rectifier potassium channel 2 KCNJ6 0.0004
1571 G protein-activated inward rectifier potassium channel 1 KCNJ3 0.0004
1268 Neuropeptide S receptor NPSR1 0.0004
5787 Angiopoietin-1 receptor TEK 0.0004
230 ATP-binding cassette transporter sub-family C member 8 ABCC8 0.0004
823 Fibroblast growth factor receptor 2 FGFR2 0.0004
5934 Cytochrome P450 26A1 CYP26A1 0.0004
751 Potassium channel subfamily K member 6 KCNK6 0.0004
6177 UDP-glucuronosyltransferase 1-10 UGT1A10 0.0004
6073 Potassium channel subfamily K member 9 KCNK9 0.0004
1360 Sphingomyelin phosphodiesterase SMPD1 0.0004
6072 Potassium channel subfamily K member 3 KCNK3 0.0004
3937 Fatty-acid amide hydrolase FAAH 0.0004
5463 Calcium-activated potassium channel subunit beta 2 KCNMB2 0.0004
172 Potassium channel subfamily K member 1 KCNK1 0.0004
40 RAF proto-oncogene serine/threonine-protein kinase RAF1 0.0004
1524 Peptidyl-prolyl cis-trans isomerase A PPIA 0.0004
6700 Peptidyl-prolyl cis-trans isomerase A ppiA 0.0004
1971 cAMP-specific 3',5'-cyclic phosphodiesterase 4A PDE4A 0.0004
951 Macrophage colony-stimulating factor 1 receptor CSF1R 0.0004
84 Nuclear receptor 0B1 NR0B1 0.0004
3957 Adenosine deaminase ADA 0.0004
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0003
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0003
937 Proto-oncogene tyrosine-protein kinase LCK LCK 0.0003
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0003
469 Annexin A1 ANXA1 0.0003
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0003
6091 Gamma-aminobutyric acid receptor subunit theta GABRQ 0.0003
2207 Rhodopsin RHO 0.0003
6086 Gamma-aminobutyric acid receptor subunit gamma-2 GABRG2 0.0003
6090 Gamma-aminobutyric acid receptor subunit pi GABRP 0.0003
6092 Gamma-aminobutyric acid receptor subunit rho-2 GABRR2 0.0003
6088 Gamma-aminobutyric acid receptor subunit gamma-3 GABRG3 0.0003
6115 Gamma-aminobutyric acid receptor subunit rho-3 GABRR3 0.0003
6087 Gamma-aminobutyric acid receptor subunit gamma-1 GABRG1 0.0003
6093 Gamma-aminobutyric acid receptor subunit delta GABRD 0.0003
6089 Gamma-aminobutyric acid receptor subunit epsilon GABRE 0.0003
142 Gamma-aminobutyric-acid receptor subunit rho-1 GABRR1 0.0003
4098 Gamma-aminobutyric-acid receptor subunit beta-1 GABRB1 0.0003
933 Proto-oncogene tyrosine-protein kinase Src SRC 0.0003
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0003
841 Gamma-aminobutyric-acid receptor subunit alpha-6 GABRA6 0.0003
530 Gamma-aminobutyric-acid receptor subunit alpha-4 GABRA4 0.0003
523 Gamma-aminobutyric-acid receptor subunit alpha-5 GABRA5 0.0002
869 Estrogen receptor beta ESR2 0.0002
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0002
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