DT-Web

DB00680 - Moricizine


Identification
Name Moricizine
Accession Number DB00680 (APRD01124)
Type small molecule
Description An antiarrhythmia agent used primarily for ventricular rhythm disturbances. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 427.517
Groups approved
Monoisotopic Weight 427.156576993
Pharmacology
Indication Used to treat irregular heartbeats (arrhythmias) and maintain a normal heart rate.
Mechanism of action Moricizine works by inhibiting the rapid inward sodium current across myocardial cell membranes.
Absorption Well absorbed, absorption is complete within 2 to 3 hours. Significant first-pass metabolism results in an absolute bioavailability of approximately 38%. Administration within 30 minutes after a meal slows the rate, but does not affect the extent of absorption, although peak plasma concentrations are reduced.
Protein binding Approximately 95%.
Biotransformation Hepatic and extensive, to at least 26 metabolites, none accounting for as much as 1% of the administered dose. Two metabolites may be pharmacologically active but are present in extremely small quantities. Moricizine induces its own metabolism (it induces hepatic cytochrome P-450 activity).
Route of elimination Less than 1% of orally administered Ethmozine(R) is excreted unchanged in the urine. Approximately 56% of the administered dose is excreted in the feces and 39% is excreted in the urine.
Toxicity Symptoms of overdose include vomiting, unconsciousness, and severe low blood pressure.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Diltiazem Increased effect/toxicity of moricizine
Ranolazine Possible additive effect on QT prolongation
Telithromycin Telithromycin may reduce clearance of Moricizine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Moricizine if Telithromycin is initiated, discontinued or dose changed.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of moricizine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of moricizine if voriconazole is initiated, discontinued or dose changed.
Food Interactions Not Available

Targets


Sodium channel protein type 5 subunit alpha
Name Sodium channel protein type 5 subunit alpha
Gene Name SCN5A
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Ahmmed GU, Hisatome I, Kurata Y, Makita N, Tanaka Y, Tanaka H, Okamura T, Sonoyama K, Furuse Y, Kato M, Yamamoto Y, Ogura K, Shimoyama M, Miake J, Sasaki N, Ogino K, Igawa O, Yoshida A, Shigemasa C: Analysis of moricizine block of sodium current in isolated guinea-pig atrial myocytes. Atrioventricular difference of moricizine block. Vascul Pharmacol. 2002 Mar;38(3):131-41. - Pubmed
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 0.4458

Predictions


Id Partner name Gene Name Score
4119 Cytochrome P450 2D6 CYP2D6 0.055
198 Sodium channel protein type 10 subunit alpha SCN10A 0.0412
6016 Cytochrome P450 2C19 CYP2C19 0.0308
4200 Cytochrome P450 1A2 CYP1A2 0.0293
4512 Cytochrome P450 3A4 CYP3A4 0.0284
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0258
4757 Cytochrome P450 2C9 CYP2C9 0.0246
587 Serum albumin ALB 0.0208
6030 Cytochrome P450 2B6 CYP2B6 0.0203
1995 Sodium channel protein type 9 subunit alpha SCN9A 0.0201
4924 Cytochrome P450 2C8 CYP2C8 0.02
465 Calmodulin CALM1 0.02
3804 Sodium channel protein type 4 subunit alpha SCN4A 0.0173
172 Potassium channel subfamily K member 1 KCNK1 0.0148
4118 Cytochrome P450 3A5 CYP3A5 0.0135
3923 Cholinesterase BCHE 0.0117
6144 Solute carrier family 22 member 2 SLC22A2 0.0105
6107 Cytochrome P450 3A7 CYP3A7 0.0098
33 Cystine/glutamate transporter SLC7A11 0.0097
1588 Multidrug resistance protein 1 ABCB1 0.0097
6145 Solute carrier family 22 member 1 SLC22A1 0.0087
6220 Aryl hydrocarbon receptor AHR 0.0082
118 Organic cation/carnitine transporter 2 SLC22A5 0.008
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0078
6024 Cytochrome P450 1A1 CYP1A1 0.0074
921 Glutamate receptor 2 GRIA2 0.007
423 Gamma-aminobutyric-acid receptor subunit alpha-2 GABRA2 0.0069
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0068
833 Organic cation/carnitine transporter 1 SLC22A4 0.0067
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0067
215 Sodium channel protein type 11 subunit alpha SCN11A 0.0067
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0064
6106 Cytochrome P450 2C18 CYP2C18 0.0061
1064 DNA (cytosine-5)-methyltransferase 1 DNMT1 0.0061
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0058
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0058
617 Muscarinic acetylcholine receptor M2 CHRM2 0.0055
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0053
6013 Cytochrome P450 2E1 CYP2E1 0.0053
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0051
6147 Solute carrier family 22 member 3 SLC22A3 0.0042
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0034
824 Sodium-dependent serotonin transporter SLC6A4 0.0033
844 Epidermal growth factor receptor EGFR 0.0032
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0031
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0029
15 Voltage-dependent T-type calcium channel subunit alpha-1I CACNA1I 0.0029
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0029
751 Potassium channel subfamily K member 6 KCNK6 0.0028
535 Voltage-dependent T-type calcium channel subunit alpha-1G CACNA1G 0.0027
713 Sodium-dependent dopamine transporter SLC6A3 0.0026
776 Bile salt export pump ABCB11 0.0024
6134 Sodium channel subunit beta-3 SCN3B 0.0024
6132 Sodium channel subunit beta-1 SCN1B 0.0024
6135 Sodium channel subunit beta-4 SCN4B 0.0024
6127 Carbonic anhydrase-related protein CA8 0.0024
6133 Sodium channel subunit beta-2 SCN2B 0.0024
6129 Carbonic anhydrase-related protein 11 CA11 0.0024
6128 Carbonic anhydrase-related protein 10 CA10 0.0024
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0023
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0022
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0022
3803 Sodium channel protein type 3 subunit alpha SCN3A 0.0021
6130 Carbonic anhydrase 13 CA13 0.002
6124 Carbonic anhydrase 5B, mitochondrial CA5B 0.002
5718 Cytochrome P450 2A6 CYP2A6 0.002
3802 Sodium channel protein type 2 subunit alpha SCN2A 0.002
6131 Carbonic anhydrase 14 CA14 0.0019
6122 Carbonic anhydrase 3 CA3 0.0018
6123 Carbonic anhydrase 5A, mitochondrial CA5A 0.0017
3007 Carbonic anhydrase 12 CA12 0.0017
4205 Carbonic anhydrase 9 CA9 0.0017
6126 Carbonic anhydrase 7 CA7 0.0016
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0014
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0014
392 Voltage-dependent P/Q-type calcium channel subunit alpha-1A CACNA1A 0.0014
964 Voltage-dependent T-type calcium channel subunit alpha-1H CACNA1H 0.0014
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0013
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0013
6020 Aldehyde oxidase AOX1 0.0013
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0013
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.0013
6142 Solute carrier family 22 member 8 SLC22A8 0.0013
592 Carbonic anhydrase 4 CA4 0.0013
295 Carbonic anhydrase 1 CA1 0.0012
3941 Amine oxidase [flavin-containing] A MAOA 0.0011
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0011
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0011
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0011
3939 Amine oxidase [flavin-containing] B MAOB 0.0011
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0011
6148 Multidrug resistance-associated protein 7 ABCC10 0.0011
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.001
357 Carbonic anhydrase 2 CA2 0.0009
2164 Multidrug resistance-associated protein 4 ABCC4 0.0009
862 Multidrug resistance-associated protein 1 ABCC1 0.0008
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