Explore a selection of our essential drug information below, or:
Identification
- Summary
Disopyramide is a class 1A antiarrhythmic agent used to treat life-threatening ventricular arrhythmias.
- Brand Names
- Norpace, Rythmodan
- Generic Name
- Disopyramide
- DrugBank Accession Number
- DB00280
- Background
A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Disopyramide (DB00280)
- Weight
- Average: 339.4745
Monoisotopic: 339.231062565 - Chemical Formula
- C21H29N3O
- Synonyms
- Disopiramida
- Disopyramide
- Disopyramidum
Pharmacology
- Indication
For the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias. It is a Class Ia antiarrhythmic drug.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Ventricular arrhythmias •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Disopyramide is an anti-arrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. At therapeutic plasma levels, disopyramide shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.
- Mechanism of action
Disopyramide is a Type 1A antiarrhythmic drug (ie, similar to procainamide and quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.
Target Actions Organism ASodium channel protein type 5 subunit alpha inhibitorHumans UMuscarinic acetylcholine receptor M1 antagonistHumans UMuscarinic acetylcholine receptor M2 antagonistHumans UMuscarinic acetylcholine receptor M3 antagonistHumans UA-type voltage-gated potassium channel KCND2 inhibitorHumans UA-type voltage-gated potassium channel KCND3 inhibitorHumans UVoltage-gated inwardly rectifying potassium channel KCNH2 inhibitorHumans UAlpha-1-acid glycoprotein 2 Not Available Humans - Absorption
Nearly complete
- Volume of distribution
Not Available
- Protein binding
50%-65%
- Metabolism
Hepatic
Hover over products below to view reaction partners
- Route of elimination
In healthy men, about 50% of a given dose of disopyramide is excreted in the urine as the unchanged drug, about 20% as the mono-N-dealkylated metabolite and 10% as the other metabolites.
- Half-life
6.7 hours (range 4-10 hours)
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
LD50=580 mg/kg in rats
- Pathways
Pathway Category Disopyramide Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Disopyramide may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Disopyramide can be increased when it is combined with Abametapir. Abatacept The metabolism of Disopyramide can be increased when combined with Abatacept. Abiraterone The serum concentration of Disopyramide can be increased when it is combined with Abiraterone. Acarbose The risk or severity of hypoglycemia can be increased when Disopyramide is combined with Acarbose. - Food Interactions
- Avoid alcohol.
- Take with or without food. The absorption is unaffected by food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Disopyramide phosphate N6BOM1935W 22059-60-5 CGDDQFMPGMYYQP-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Dicorantil (Sanofi) / Isorythm (SERP) / Lispine (Sawai Seiyaku) / Ritmodan (Sanofi)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Disopyramide Phosphate ER Capsule, extended release 150 mg/1 Oral Ethex Corporation 2007-02-23 Not applicable US 
Norpace Capsule, gelatin coated 150 mg/1 Oral Physicians Total Care, Inc. 1982-07-20 2012-06-30 US Norpace Capsule, gelatin coated 150 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 1977-09-01 Not applicable US Norpace Capsule, gelatin coated 150 mg/1 Oral Carilion Materials Management 1982-07-20 Not applicable US Norpace Capsule, gelatin coated 100 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 1977-09-01 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Disopyramide Phosphate Capsule 100 mg/1 Oral AvKARE 2014-01-03 Not applicable US Disopyramide Phosphate Capsule 150 mg/1 Oral Teva Pharmaceuticals USA, Inc. 1990-09-30 Not applicable US 
Disopyramide Phosphate Capsule 150 mg/1 Oral Physicians Total Care, Inc. 1985-05-31 2002-06-30 US Disopyramide Phosphate Capsule 100 mg/1 Oral Mayne Pharma Inc. 2016-08-03 2020-03-31 US Disopyramide Phosphate Capsule 100 mg/1 Oral Med Pharma Co., Ltd. 2011-07-05 2012-07-18 US
Categories
- ATC Codes
- C01BA03 — Disopyramide
- Drug Categories
- Agents producing tachycardia
- Antiarrhythmic agents
- Antiarrhythmics, Class I
- Antiarrhythmics, Class Ia
- Anticholinergic Agents
- Blood Glucose Lowering Agents
- Cardiac Therapy
- Cardiovascular Agents
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Highest Risk QTc-Prolonging Agents
- Hypoglycemia-Associated Agents
- Membrane Transport Modulators
- Muscarinic Antagonists
- Negative Inotrope
- OCT1 inhibitors
- OCT2 Inhibitors
- Pyridines
- QTc Prolonging Agents
- Sodium Channel Blockers
- Voltage-Gated Sodium Channel Blockers
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pheniramines. These are compounds containing a pheniramine moiety, which is structurally characterized by the presence of a 2-benzylpyridine linked to an dimethyl(propyl)amine to form a dimethyl[3-phenyl-3-(pyridin-2-yl)propyl]amine skeleton.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Pheniramines
- Direct Parent
- Pheniramines
- Alternative Parents
- Aralkylamines / Benzene and substituted derivatives / Heteroaromatic compounds / Trialkylamines / Carboximidic acids / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Hydrocarbon derivatives
- Substituents
- Amine / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carboximidic acid / Carboximidic acid derivative / Heteroaromatic compound / Hydrocarbon derivative / Monocyclic benzene moiety
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- tertiary amino compound, monocarboxylic acid amide, pyridines (CHEBI:4657)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- GFO928U8MQ
- CAS number
- 3737-09-5
- InChI Key
- UVTNFZQICZKOEM-UHFFFAOYSA-N
- InChI
- InChI=1S/C21H29N3O/c1-16(2)24(17(3)4)15-13-21(20(22)25,18-10-6-5-7-11-18)19-12-8-9-14-23-19/h5-12,14,16-17H,13,15H2,1-4H3,(H2,22,25)
- IUPAC Name
- 4-[bis(propan-2-yl)amino]-2-phenyl-2-(pyridin-2-yl)butanamide
- SMILES
- CC(C)N(CCC(C(N)=O)(C1=CC=CC=C1)C1=NC=CC=C1)C(C)C
References
- Synthesis Reference
Cusic, J.W. and Sause, H.W.; U.S. Patent 3,225,054; December 21,1965; assigned to G.D. Searle & Co.
US3225054- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014425
- KEGG Drug
- D00303
- KEGG Compound
- C06965
- PubChem Compound
- 3114
- PubChem Substance
- 46508226
- ChemSpider
- 3002
- BindingDB
- 50028893
- 3541
- ChEBI
- 4657
- ChEMBL
- CHEMBL517
- Therapeutic Targets Database
- DAP000504
- PharmGKB
- PA449373
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Disopyramide
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Recruiting Not Available Obstructive Hypertrophic Cardiomyopathy 1 somestatus stop reason just information to hide Not Available Unknown Status Treatment Atrial Fibrillation / Quality of Life (QOL) 1 somestatus stop reason just information to hide 3 Completed Treatment Arrhythmia / Atrial Fibrillation / Cardiovascular Disease (CVD) 1 somestatus stop reason just information to hide 3 Terminated Treatment Atrial Fibrillation / Heart Failure 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Kv pharmaceutical co
- Gd searle llc
- Interpharm inc
- Ivax pharmaceuticals inc sub teva pharmaceuticals usa
- Mutual pharmaceutical co inc
- Mylan pharmaceuticals inc
- Sandoz inc
- Superpharm corp
- Teva pharmaceuticals usa inc
- Watson laboratories inc
- Packagers
- Amerisource Health Services Corp.
- Ethex Corp.
- GD Searle LLC
- Kaiser Foundation Hospital
- KV Pharmaceutical Co.
- Murfreesboro Pharmaceutical Nursing Supply
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmacia Inc.
- Physicians Total Care Inc.
- Sandhills Packaging Inc.
- Teva Pharmaceutical Industries Ltd.
- Watson Pharmaceuticals
- Dosage Forms
Form Route Strength Capsule, coated Oral 100 mg Capsule Oral 100.000 mg Tablet Oral 250.000 mg Capsule Oral 100 mg/1 Capsule Oral 150 mg/1 Capsule, extended release Oral 150 mg/1 Capsule, gelatin coated Oral 100 mg/1 Capsule, gelatin coated Oral 150 mg/1 Capsule, extended release Oral 100 mg/1 Tablet, extended release Oral 150 mg Tablet Oral 250 MG Capsule Oral 100 mg Capsule Oral 150 mg Tablet, extended release Oral 250 mg Tablet, extended release Oral 250 mg / srt - Prices
Unit description Cost Unit Norpace CR 150 mg 12 Hour Capsule 2.35USD capsule Norpace cr 150 mg capsule 2.26USD capsule Norpace CR 100 mg 12 Hour Capsule 1.98USD capsule Norpace 150 mg capsule 1.94USD capsule Norpace cr 100 mg capsule 1.91USD capsule Norpace 100 mg capsule 1.62USD capsule Disopyramide Phosphate 150 mg capsule 0.96USD capsule Disopyramide 150 mg capsule 0.82USD capsule Disopyramide Phosphate 100 mg capsule 0.72USD capsule Disopyramide 100 mg capsule 0.69USD capsule Rythmodan 150 mg Capsule 0.43USD capsule Rythmodan 100 mg Capsule 0.3USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 94.5-95 °C Cusic, J.W. and Sause, H.W.; U.S. Patent 3,225,054; December 21,1965; assigned to G.D. Searle & Co. water solubility 44.9 mg/L Not Available logP 2.58 MANNHOLD,R ET AL. (1993) - Predicted Properties
Property Value Source Water Solubility 0.0493 mg/mL ALOGPS logP 3.21 ALOGPS logP 3.47 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 16.19 Chemaxon pKa (Strongest Basic) 10.42 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 59.22 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 102.3 m3·mol-1 Chemaxon Polarizability 38.82 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9529 Blood Brain Barrier + 0.9508 Caco-2 permeable + 0.557 P-glycoprotein substrate Substrate 0.5492 P-glycoprotein inhibitor I Non-inhibitor 0.8677 P-glycoprotein inhibitor II Non-inhibitor 0.8535 Renal organic cation transporter Inhibitor 0.5702 CYP450 2C9 substrate Non-substrate 0.7975 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.6906 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.8236 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8626 Ames test Non AMES toxic 0.8258 Carcinogenicity Non-carcinogens 0.8873 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.9764 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.996 hERG inhibition (predictor II) Inhibitor 0.6168
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 194.1952717 predictedDarkChem Lite v0.1.0 [M-H]- 180.42598 predictedDeepCCS 1.0 (2019) [M+H]+ 194.7155717 predictedDarkChem Lite v0.1.0 [M+H]+ 182.78398 predictedDeepCCS 1.0 (2019) [M+Na]+ 193.9767717 predictedDarkChem Lite v0.1.0 [M+Na]+ 189.6569 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Pore-forming subunit of Nav1.5, a voltage-gated sodium (Nav) channel that directly mediates the depolarizing phase of action potentials in excitable membranes. Navs, also called VGSCs (voltage-gated sodium channels) or VDSCs (voltage-dependent sodium channels), operate by switching between closed and open conformations depending on the voltage difference across the membrane. In the open conformation they allow Na(+) ions to selectively pass through the pore, along their electrochemical gradient. The influx of Na(+) ions provokes membrane depolarization, initiating the propagation of electrical signals throughout cells and tissues (PubMed:1309946, PubMed:21447824, PubMed:23085483, PubMed:23420830, PubMed:25370050, PubMed:26279430, PubMed:26392562, PubMed:26776555). Nav1.5 is the predominant sodium channel expressed in myocardial cells and it is responsible for the initial upstroke of the action potential in cardiac myocytes, thereby initiating the heartbeat (PubMed:11234013, PubMed:11804990, PubMed:12569159, PubMed:1309946). Required for normal electrical conduction including formation of the infranodal ventricular conduction system and normal action potential configuration, as a result of its interaction with XIRP2 (By similarity)
- Specific Function
- ankyrin binding
- Gene Name
- SCN5A
- Uniprot ID
- Q14524
- Uniprot Name
- Sodium channel protein type 5 subunit alpha
- Molecular Weight
- 226937.475 Da
References
- Sugao M, Fujiki A, Nishida K, Sakabe M, Tsuneda T, Iwamoto J, Mizumaki K, Inoue H: Repolarization dynamics in patients with idiopathic ventricular fibrillation: pharmacological therapy with bepridil and disopyramide. J Cardiovasc Pharmacol. 2005 Jun;45(6):545-9. [Article]
- Fujiki A, Sugao M, Nishida K, Sakabe M, Tsuneda T, Mizumaki K, Inoue H: Repolarization abnormality in idiopathic ventricular fibrillation: assessment using 24-hour QT-RR and QaT-RR relationships. J Cardiovasc Electrophysiol. 2004 Jan;15(1):59-63. [Article]
- Shimizu W, Antzelevitch C, Suyama K, Kurita T, Taguchi A, Aihara N, Takaki H, Sunagawa K, Kamakura S: Effect of sodium channel blockers on ST segment, QRS duration, and corrected QT interval in patients with Brugada syndrome. J Cardiovasc Electrophysiol. 2000 Dec;11(12):1320-9. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- CHRM1
- Uniprot ID
- P11229
- Uniprot Name
- Muscarinic acetylcholine receptor M1
- Molecular Weight
- 51420.375 Da
References
- Yamamoto N, Ozaki T, Keida Y, Ohtsuka M, Goto T: A comparison of the binding characteristics of class I antiarrhythmic agents for human muscarinic m1-m3 receptors. J Cardiovasc Pharmacol. 1999 Jul;34(1):53-9. [Article]
- Ishida Y, Mizukami M, Taniguchi T, Satake N, Fujiwara M, Shibata S: Anticholinergic action of disopyramide in intestinal smooth muscle of the guinea pig: inhibition of muscarinic receptors (M1 and M2). Jpn J Pharmacol. 1990 Feb;52(2):363-70. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol
- Specific Function
- arrestin family protein binding
- Gene Name
- CHRM2
- Uniprot ID
- P08172
- Uniprot Name
- Muscarinic acetylcholine receptor M2
- Molecular Weight
- 51714.605 Da
References
- Yamamoto N, Ozaki T, Keida Y, Ohtsuka M, Goto T: A comparison of the binding characteristics of class I antiarrhythmic agents for human muscarinic m1-m3 receptors. J Cardiovasc Pharmacol. 1999 Jul;34(1):53-9. [Article]
- Ishida Y, Mizukami M, Taniguchi T, Satake N, Fujiwara M, Shibata S: Anticholinergic action of disopyramide in intestinal smooth muscle of the guinea pig: inhibition of muscarinic receptors (M1 and M2). Jpn J Pharmacol. 1990 Feb;52(2):363-70. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- acetylcholine binding
- Gene Name
- CHRM3
- Uniprot ID
- P20309
- Uniprot Name
- Muscarinic acetylcholine receptor M3
- Molecular Weight
- 66127.445 Da
References
- Yamamoto N, Ozaki T, Keida Y, Ohtsuka M, Goto T: A comparison of the binding characteristics of class I antiarrhythmic agents for human muscarinic m1-m3 receptors. J Cardiovasc Pharmacol. 1999 Jul;34(1):53-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:11507158, PubMed:14623880, PubMed:14695263, PubMed:14980201, PubMed:15454437, PubMed:16934482, PubMed:19171772, PubMed:24501278, PubMed:24811166, PubMed:34552243, PubMed:35597238). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:14623880, PubMed:14980201, PubMed:15454437, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity). Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state) (PubMed:35597238)
- Specific Function
- A-type (transient outward) potassium channel activity
- Gene Name
- KCND2
- Uniprot ID
- Q9NZV8
- Uniprot Name
- A-type voltage-gated potassium channel KCND2
- Molecular Weight
- 70535.825 Da
References
- Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Pore-forming (alpha) subunit of voltage-gated A-type potassium channels that mediates transmembrane potassium transport in excitable membranes, in brain and heart (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). In cardiomyocytes, may generate the transient outward potassium current I(To) (By similarity). In neurons, may conduct the transient subthreshold somatodendritic A-type potassium current (ISA) (By similarity). Kinetics properties are characterized by fast activation at subthreshold membrane potentials, rapid inactivation, and quick recovery from inactivation (PubMed:10200233, PubMed:17187064, PubMed:21349352, PubMed:22457051, PubMed:23280837, PubMed:23280838, PubMed:34997220, PubMed:9843794). Channel properties are modulated by interactions with regulatory subunits (PubMed:17187064, PubMed:34997220). Interaction with the regulatory subunits KCNIP1 or KCNIP2 modulates the channel gating kinetics namely channel activation and inactivation kinetics and rate of recovery from inactivation (PubMed:17187064, PubMed:34997220). Likewise, interaction with DPP6 modulates the channel gating kinetics namely channel activation and inactivation kinetics (PubMed:34997220)
- Specific Function
- A-type (transient outward) potassium channel activity
- Gene Name
- KCND3
- Uniprot ID
- Q9UK17
- Uniprot Name
- A-type voltage-gated potassium channel KCND3
- Molecular Weight
- 73450.53 Da
References
- Casis O, Sanchez-Chapula JA: Disopyramide, imipramine, and amitriptyline bind to a common site on the transient outward K+ channel. J Cardiovasc Pharmacol. 1998 Oct;32(4):521-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Characterized by unusual gating kinetics by producing relatively small outward currents during membrane depolarization and large inward currents during subsequent repolarization which reflect a rapid inactivation during depolarization and quick recovery from inactivation but slow deactivation (closing) during repolarization (PubMed:10219239, PubMed:10753933, PubMed:10790218, PubMed:10837251, PubMed:11997281, PubMed:12063277, PubMed:18559421, PubMed:22314138, PubMed:22359612, PubMed:26363003, PubMed:27916661, PubMed:9230439, PubMed:9351446, PubMed:9765245). Channel properties are modulated by cAMP and subunit assembly (PubMed:10837251). Forms a stable complex with KCNE1 or KCNE2, and that this heteromultimerization regulates inward rectifier potassium channel activity (PubMed:10219239, PubMed:9230439)
- Specific Function
- delayed rectifier potassium channel activity
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Voltage-gated inwardly rectifying potassium channel KCNH2
- Molecular Weight
- 126653.52 Da
References
- Chiu PJ, Marcoe KF, Bounds SE, Lin CH, Feng JJ, Lin A, Cheng FC, Crumb WJ, Mitchell R: Validation of a [3H]astemizole binding assay in HEK293 cells expressing HERG K+ channels. J Pharmacol Sci. 2004 Jul;95(3):311-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Functions as a transport protein in the blood stream. Binds various hydrophobic ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM2
- Uniprot ID
- P19652
- Uniprot Name
- Alpha-1-acid glycoprotein 2
- Molecular Weight
- 23602.43 Da
References
- Herve F, Duche JC, d'Athis P, Marche C, Barre J, Tillement JP: Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycoprotein. Pharmacogenetics. 1996 Oct;6(5):403-15. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- Zhang L, Fitzloff JF, Engel LC, Cook CS: Species difference in stereoselective involvement of CYP3A in the mono-N-dealkylation of disopyramide. Xenobiotica. 2001 Feb;31(2):73-83. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Echizen H, Tanizaki M, Tatsuno J, Chiba K, Berwick T, Tani M, Gonzalez FJ, Ishizaki T: Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans. Drug Metab Dispos. 2000 Aug;28(8):937-44. [Article]
- Zhang L, Fitzloff JF, Engel LC, Cook CS: Species difference in stereoselective involvement of CYP3A in the mono-N-dealkylation of disopyramide. Xenobiotica. 2001 Feb;31(2):73-83. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Other/unknown
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- Chu JS, Kishion S, Nomura A, Miyazaki K: Serum alpha 1-acid glycoprotein, sialic acid, and protein binding of disopyramide in normal subjects and cardiac patients. Zhongguo Yao Li Xue Bao. 1997 Sep;18(5):408-10. [Article]
- Hanada K, Ohta T, Hirai M, Arai M, Ogata H: Enantioselective binding of propranolol, disopyramide, and verapamil to human alpha(1)-acid glycoprotein. J Pharm Sci. 2000 Jun;89(6):751-7. [Article]
- Nakagawa T, Kishino S, Itoh S, Sugawara M, Miyazaki K: Differential binding of disopyramide and warfarin enantiomers to human alpha(1)-acid glycoprotein variants. Br J Clin Pharmacol. 2003 Dec;56(6):664-9. [Article]
- Haughey DB, Steinberg I, Lee MH: Protein binding of disopyramide--displacement by mono-N-dealkyldisopyramide and variation with source of alpha-1-acid glycoprotein. J Pharm Pharmacol. 1985 Apr;37(4):285-8. [Article]
- Brunner F, Muller WE: Prazosin binding to human alpha 1-acid glycoprotein (orosomucoid), human serum albumin, and human serum. Further characterization of the 'single drug binding site' of orosomucoid. J Pharm Pharmacol. 1985 May;37(5):305-9. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
- Specific Function
- (R)-carnitine transmembrane transporter activity
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- Zhang L, Schaner ME, Giacomini KM: Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa). J Pharmacol Exp Ther. 1998 Jul;286(1):354-61. [Article]
- Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [Article]
- Zhang S, Lovejoy KS, Shima JE, Lagpacan LL, Shu Y, Lapuk A, Chen Y, Komori T, Gray JW, Chen X, Lippard SJ, Giacomini KM: Organic cation transporters are determinants of oxaliplatin cytotoxicity. Cancer Res. 2006 Sep 1;66(17):8847-57. doi: 10.1158/0008-5472.CAN-06-0769. [Article]
- Li S, Chen Y, Zhang S, More SS, Huang X, Giacomini KM: Role of organic cation transporter 1, OCT1 in the pharmacokinetics and toxicity of cis-diammine(pyridine)chloroplatinum(II) and oxaliplatin in mice. Pharm Res. 2011 Mar;28(3):610-25. doi: 10.1007/s11095-010-0312-6. Epub 2010 Nov 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- acetylcholine transmembrane transporter activity
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- Urakami Y, Okuda M, Masuda S, Akazawa M, Saito H, Inui K: Distinct characteristics of organic cation transporters, OCT1 and OCT2, in the basolateral membrane of renal tubules. Pharm Res. 2001 Nov;18(11):1528-34. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 21, 2024 12:51