DT-Web

DB00422 - Methylphenidate


Identification
Name Methylphenidate
Accession Number DB00422 (APRD00657)
Type small molecule
Description A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 233.3062
Groups approved
Monoisotopic Weight 233.141578857
Pharmacology
Indication For use as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity.
Mechanism of action Methylphenidate blocks dopamine uptake in central adrenergic neurons by blocking dopamine transport or carrier proteins. Methylphenidate acts at the brain stem arousal system and the cerebral cortex and causes increased sympathomimetic activity in the central nervous system. Alteration of serotonergic pathways via changes in dopamine transport may result.
Absorption Readily absorbed in a biphasic manner when orally administered (tablets) to children diagnosed with ADHD and to healthy adults. In children and adults males, after administration of a single oral dose of Ritalin LA and Ritalin given in two doses 4 hours apart, peak plasma concentration is reached approximately 2 hours for the first phase and 5-6 hours for the second phase. The absolute oral bioavailability of methylphenidate in children was 22?8% for d-methylphenidate and 5?3% for l-methylphenidate. These low values suggest that methylphenidate is highly metabolized presystemically.
Protein binding Binding to plasma proteins is low (10%-33%).
Biotransformation Methylphenidate is hepatically metabolized. More specifically, it is rapidly and extensively metabolized by carboxylesterase CES1A1. Via this enzyme, methylphenidate undergoes de-esterification to ritalinic acid (a-phenyl-2-piperidine acetic acid, PPAA), which has little to no pharmacologic activity.
Route of elimination After oral administration of an immediate release formulation of methylphenidate, 78%-97% of the dose is excreted in the urine and 1%-3% in the feces in the form of metabolites within 48-96 hours. Only small quantities (<1%) of unchanged methylphenidate appear in the urine. Most of the dose is excreted in the urine as ritalinic acid (60%-86%), the remainder being accounted for by minor metabolites.
Toxicity Symptoms of overdose include vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, and dryness of mucous membranes. LD50=190mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Carbamazepine Carbamazepine may decrease the effect of methylphendiate.
Cyclosporine Methylphenidate increases the effect and toxicity of cyclosporine
Guanethidine Methylphenidate may decrease the effect of guanethidine.
Isocarboxazid Possible hypertensive crisis with this combination
Phenelzine Possible hypertensive crisis with this combination
Rasagiline Possible hypertensive crisis with this combination.
Trandolapril Methylphenidate may antagonize the antihypertensive effect of Trandolapril. Monitor for changes in blood pressure if Methylphenidate is initiated, discontinued or dose changed.
Tranylcypromine The MAO inhibitor, Tranylcypromine, may increase the vasopressor effect of Methylphenidate. Concomitant therapy is contraindicated.
Food Interactions
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take on empty stomach: 1 hour before or 2 hours after meals.
  • Avoid alcohol.

Targets


Sodium-dependent dopamine transporter
Name Sodium-dependent dopamine transporter
Gene Name SLC6A3
Pharmacological action yes
Actions inhibitor
References
  • Volkow ND, Fowler JS, Gatley SJ, Dewey SL, Wang GJ, Logan J, Ding YS, Franceschi D, Gifford A, Morgan A, Pappas N, King P: Comparable changes in synaptic dopamine induced by methylphenidate and by cocaine in the baboon brain. Synapse. 1999 Jan;31(1):59-66. - Pubmed
  • Wayment HK, Deutsch H, Schweri MM, Schenk JO: Effects of methylphenidate analogues on phenethylamine substrates for the striatal dopamine transporter: potential as amphetamine antagonists? J Neurochem. 1999 Mar;72(3):1266-74. - Pubmed
  • Dresel SH, Kung MP, Huang X, Plossl K, Hou C, Shiue CY, Karp J, Kung HF: In vivo imaging of serotonin transporters with [99mTc]TRODAT-1 in nonhuman primates. Eur J Nucl Med. 1999 Apr;26(4):342-7. - Pubmed
  • Volkow ND, Wang GJ, Fowler JS, Fischman M, Foltin R, Abumrad NN, Gatley SJ, Logan J, Wong C, Gifford A, Ding YS, Hitzemann R, Pappas N: Methylphenidate and cocaine have a similar in vivo potency to block dopamine transporters in the human brain. Life Sci. 1999;65(1):PL7-12. - Pubmed
  • Izenwasser S, Coy AE, Ladenheim B, Loeloff RJ, Cadet JL, French D: Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine. Eur J Pharmacol. 1999 Jun 4;373(2-3):187-93. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. - Pubmed
  • Viggiano D, Vallone D, Sadile A: Dysfunctions in dopamine systems and ADHD: evidence from animals and modeling. Neural Plast. 2004;11(1-2):97-114. - Pubmed
  • Tilley MR, Gu HH: The effects of methylphenidate on knockin mice with a methylphenidate-resistant dopamine transporter. J Pharmacol Exp Ther. 2008 Nov;327(2):554-60. Epub 2008 Aug 12. - Pubmed
DTHybrid score 0.5439
Sodium-dependent noradrenaline transporter
Name Sodium-dependent noradrenaline transporter
Gene Name SLC6A2
Pharmacological action unknown
Actions inhibitor
References
  • Yang L, Wang YF, Li J, Faraone SV: Association of norepinephrine transporter gene with methylphenidate response. J Am Acad Child Adolesc Psychiatry. 2004 Sep;43(9):1154-8. - Pubmed
  • Williard RL, Middaugh LD, Zhu HJ, Patrick KS: Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity. Behav Pharmacol. 2007 Feb;18(1):39-51. - Pubmed
  • Chuhan YS, Taukulis HK: Impairment of single-trial memory formation by oral methylphenidate in the rat. Neurobiol Learn Mem. 2006 Mar;85(2):125-31. Epub 2005 Oct 24. - Pubmed
  • Gray JD, Punsoni M, Tabori NE, Melton JT, Fanslow V, Ward MJ, Zupan B, Menzer D, Rice J, Drake CT, Romeo RD, Brake WG, Torres-Reveron A, Milner TA: Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress. J Neurosci. 2007 Jul 4;27(27):7196-207. - Pubmed
  • Sandoval V, Riddle EL, Ugarte YV, Hanson GR, Fleckenstein AE: Methamphetamine-induced rapid and reversible changes in dopamine transporter function: an in vitro model. J Neurosci. 2001 Feb 15;21(4):1413-9. - Pubmed
  • Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. - Pubmed
  • Tilley MR, Gu HH: The effects of methylphenidate on knockin mice with a methylphenidate-resistant dopamine transporter. J Pharmacol Exp Ther. 2008 Nov;327(2):554-60. Epub 2008 Aug 12. - Pubmed
DTHybrid score 0.5952
Sodium-dependent serotonin transporter
Name Sodium-dependent serotonin transporter
Gene Name SLC6A4
Pharmacological action unknown
Actions inhibitor
References
  • Dresel SH, Kung MP, Huang X, Plossl K, Hou C, Shiue CY, Karp J, Kung HF: In vivo imaging of serotonin transporters with [99mTc]TRODAT-1 in nonhuman primates. Eur J Nucl Med. 1999 Apr;26(4):342-7. - Pubmed
  • Izenwasser S, Coy AE, Ladenheim B, Loeloff RJ, Cadet JL, French D: Chronic methylphenidate alters locomotor activity and dopamine transporters differently from cocaine. Eur J Pharmacol. 1999 Jun 4;373(2-3):187-93. - Pubmed
  • Stehouwer JS, Jarkas N, Zeng F, Voll RJ, Williams L, Owens MJ, Votaw JR, Goodman MM: Synthesis, radiosynthesis, and biological evaluation of carbon-11 labeled 2beta-carbomethoxy-3beta-(3'-((Z)-2-haloethenyl)phenyl)nortropanes: candidate radioligands for in vivo imaging of the serotonin transporter with positron emission tomography. J Med Chem. 2006 Nov 16;49(23):6760-7. - Pubmed
DTHybrid score 0.4376

Enzymes


Cytochrome P450 2D6
Name Cytochrome P450 2D6
Gene Name CYP2D6
Actions substrate,inhibitor
References
  • Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. - Pubmed
DTHybrid score 0.391
Carboxylesterase 1A1
Name Carboxylesterase 1A1
Gene Name Not Available
Actions substrate
References
  • FDA label -
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
4512 Cytochrome P450 3A4 CYP3A4 0.1806
6016 Cytochrome P450 2C19 CYP2C19 0.105
556 Alpha-1A adrenergic receptor ADRA1A 0.1048
4200 Cytochrome P450 1A2 CYP1A2 0.0988
1588 Multidrug resistance protein 1 ABCB1 0.0959
4757 Cytochrome P450 2C9 CYP2C9 0.0949
131 Synaptic vesicular amine transporter SLC18A2 0.0913
492 Histamine H1 receptor HRH1 0.0875
3941 Amine oxidase [flavin-containing] A MAOA 0.0856
502 5-hydroxytryptamine 2A receptor HTR2A 0.0737
6030 Cytochrome P450 2B6 CYP2B6 0.0725
3939 Amine oxidase [flavin-containing] B MAOB 0.0714
318 Alpha-2A adrenergic receptor ADRA2A 0.0649
632 Alpha-1B adrenergic receptor ADRA1B 0.0608
590 5-hydroxytryptamine 2C receptor HTR2C 0.059
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0584
4118 Cytochrome P450 3A5 CYP3A5 0.0545
4924 Cytochrome P450 2C8 CYP2C8 0.0498
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0466
6013 Cytochrome P450 2E1 CYP2E1 0.0459
6107 Cytochrome P450 3A7 CYP3A7 0.0448
766 Beta-2 adrenergic receptor ADRB2 0.038
436 5-hydroxytryptamine 2B receptor HTR2B 0.0378
193 Beta-1 adrenergic receptor ADRB1 0.0373
1636 Trace amine-associated receptor 1 TAAR1 0.0344
831 D(2) dopamine receptor DRD2 0.0344
320 5-hydroxytryptamine 1A receptor HTR1A 0.0336
629 Alpha-2B adrenergic receptor ADRA2B 0.0314
5718 Cytochrome P450 2A6 CYP2A6 0.0273
51 Muscarinic acetylcholine receptor M3 CHRM3 0.027
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0266
617 Muscarinic acetylcholine receptor M2 CHRM2 0.026
6144 Solute carrier family 22 member 2 SLC22A2 0.0257
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0252
341 5-hydroxytryptamine 3 receptor HTR3A 0.0246
6024 Cytochrome P450 1A1 CYP1A1 0.0246
378 Alpha-2C adrenergic receptor ADRA2C 0.024
6145 Solute carrier family 22 member 1 SLC22A1 0.0238
118 Organic cation/carnitine transporter 2 SLC22A5 0.0238
23 D(1A) dopamine receptor DRD1 0.0234
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0229
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0219
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0214
6147 Solute carrier family 22 member 3 SLC22A3 0.0213
1656 CYP2B protein CYP2B 0.0207
847 Mu-type opioid receptor OPRM1 0.0198
220 Sodium channel protein type 5 subunit alpha SCN5A 0.0197
467 Delta-type opioid receptor OPRD1 0.0191
696 Kappa-type opioid receptor OPRK1 0.0187
3923 Cholinesterase BCHE 0.0177
789 Alpha-1D adrenergic receptor ADRA1D 0.0176
6106 Cytochrome P450 2C18 CYP2C18 0.0164
587 Serum albumin ALB 0.016
1517 Beta-3 adrenergic receptor ADRB3 0.0153
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0147
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0127
6432 Transporter snf 0.0123
474 Acetylcholinesterase ACHE 0.0122
6182 Cytochrome P450 2J2 CYP2J2 0.0119
982 Cocaine- and amphetamine-regulated transcript protein CARTPT 0.011
1757 Myeloperoxidase MPO 0.0109
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0103
813 Neuronal acetylcholine receptor subunit alpha-2 CHRNA2 0.01
833 Organic cation/carnitine transporter 1 SLC22A4 0.0099
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0098
638 D(3) dopamine receptor DRD3 0.0096
20 Prostaglandin G/H synthase 1 PTGS1 0.009
458 Neuronal acetylcholine receptor subunit alpha-10 CHRNA10 0.0086
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0079
6079 Neuronal acetylcholine receptor subunit alpha-3 CHRNA3 0.0079
432 D(4) dopamine receptor DRD4 0.0079
885 5-hydroxytryptamine 1B receptor HTR1B 0.0076
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0074
4120 NADPH--cytochrome P450 reductase POR 0.0071
94 5-hydroxytryptamine 4 receptor HTR4 0.0071
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0068
163 D(1B) dopamine receptor DRD5 0.0066
862 Multidrug resistance-associated protein 1 ABCC1 0.0066
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0065
465 Calmodulin CALM1 0.0065
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0062
725 5-hydroxytryptamine 1D receptor HTR1D 0.0061
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0058
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0058
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0055
1898 Cytochrome P450 1B1 CYP1B1 0.0053
731 HIV-1 protease HIV-1 protease 0.0052
124 Histamine H2 receptor HRH2 0.0051
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.005
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0049
482 Glycine receptor subunit alpha-1 GLRA1 0.0048
904 Glutathione S-transferase P GSTP1 0.0047
174 Sigma 1-type opioid receptor SIGMAR1 0.0046
2112 Toll-like receptor 9 TLR9 0.0044
2981 Phospholipase A2, membrane associated PLA2G2A 0.0044
828 Phenylalanine-4-hydroxylase PAH 0.0043
3109 Phenylalanine-4-hydroxylase phhA 0.0043
439 Glutamate [NMDA] receptor subunit epsilon-4 GRIN2D 0.0043
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.0042
1729 Solute carrier family 22 member 6 SLC22A6 0.0041
1360 Sphingomyelin phosphodiesterase SMPD1 0.0039
6086 Gamma-aminobutyric acid receptor subunit gamma-2 GABRG2 0.0039
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0039
776 Bile salt export pump ABCB11 0.0039
360 Ribonucleoside-diphosphate reductase large subunit RRM1 0.0039
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0038
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0038
319 Opioid receptor, sigma 1 OPRS1 0.0038
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0036
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0036
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0035
4099 Gamma-aminobutyric-acid receptor subunit beta-3 GABRB3 0.0035
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0034
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0034
380 Cytochrome P450 17A1 CYP17A1 0.0034
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0033
6506 Stathmin-4 STMN4 0.0033
173 Toll-like receptor 7 TLR7 0.0033
817 DNA topoisomerase 2-alpha TOP2A 0.0033
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0032
1618 High affinity nerve growth factor receptor NTRK1 0.0031
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0031
4199 Sphingosine 1-phosphate receptor Edg-8 S1PR5 0.0031
153 Dopamine beta-hydroxylase DBH 0.003
620 Bifunctional dihydrofolate reductase-thymidylate synthase Not Available 0.003
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0029
716 5-hydroxytryptamine 7 receptor HTR7 0.0029
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0029
565 Extracellular calcium-sensing receptor CASR 0.0028
6031 Cytochrome P450 3A43 CYP3A43 0.0028
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0028
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0027
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0027
1256 5-hydroxytryptamine 6 receptor HTR6 0.0027
1995 Sodium channel protein type 9 subunit alpha SCN9A 0.0027
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0026
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0026
3804 Sodium channel protein type 4 subunit alpha SCN4A 0.0026
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0025
3811 Cytochrome P450 19A1 CYP19A1 0.0025
2164 Multidrug resistance-associated protein 4 ABCC4 0.0025
805 Cytochrome P450 11B1, mitochondrial CYP11B1 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
750 Voltage-dependent calcium channel gamma-1 subunit CACNG1 0.0024
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0024
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0024
3810 Catechol O-methyltransferase COMT 0.0024
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0024
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0023
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0023
6151 Monocarboxylate transporter 10 SLC16A10 0.0023
385 Potassium-transporting ATPase alpha chain 1 ATP4A 0.0022
504 Mast/stem cell growth factor receptor KIT 0.0022
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
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0021
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0021
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
6148 Multidrug resistance-associated protein 7 ABCC10 0.0019
871 Glucocorticoid receptor NR3C1 0.0019
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 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
528 5-hydroxytryptamine 1E receptor HTR1E 0.0018
748 5'-AMP-activated protein kinase catalytic subunit alpha-1 PRKAA1 0.0018
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0017
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 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
3947 Xanthine dehydrogenase/oxidase XDH 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
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0015
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0015
4604 Liver carboxylesterase 1 CES1 0.0015
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0015
1050 Bile salt sulfotransferase SULT2A1 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
1010 Cytochrome P450 51A1 CYP51A1 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
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0011
1561 Troponin C, slow skeletal and cardiac muscles TNNC1 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
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0011
164 Histamine H4 receptor HRH4 0.0011
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
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
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 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
6137 Multidrug resistance-associated protein 6 ABCC6 0.0008
866 Large neutral amino acids transporter small subunit 2 SLC7A8 0.0007
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
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
245 Large neutral amino acids transporter small subunit 1 SLC7A5 0.0007
4773 Deoxycytidine kinase DCK 0.0007
2222 Equilibrative nucleoside transporter 1 SLC29A1 0.0007
1992 Vitamin D-binding protein GC 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
7 Nitric oxide synthase, inducible NOS2 0.0007
6037 Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma PDE6G 0.0007
737 Mineralocorticoid receptor NR3C2 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
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
6146 High affinity copper uptake protein 1 SLC31A1 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
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
291 Nitric-oxide synthase, endothelial NOS3 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
6172 ATP-binding cassette sub-family B member 8, mitochondrial ABCB8 0.0004
6073 Potassium channel subfamily K member 9 KCNK9 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
337 NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial NDUFS7 0.0004
214 NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NDUFS3 0.0004
803 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial NDUFS2 0.0004
3957 Adenosine deaminase ADA 0.0004
6168 Solute carrier family 22 member 16 SLC22A16 0.0003
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0003
937 Proto-oncogene tyrosine-protein kinase LCK LCK 0.0003
6861 Alcohol dehydrogenase [NADP+] AKR1A1 0.0003
6140 Ileal sodium/bile acid cotransporter SLC10A2 0.0003
469 Annexin A1 ANXA1 0.0003
6091 Gamma-aminobutyric acid receptor subunit theta GABRQ 0.0003
2207 Rhodopsin RHO 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
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
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0002
869 Estrogen receptor beta ESR2 0.0002
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0002
76 Nitric-oxide synthase, brain NOS1 0.0002
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