Identification
- Generic Name
- Debrisoquine
- DrugBank Accession Number
- DB04840
- Background
An adrenergic neuron-blocking drug similar in effects to guanethidine. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Debrisoquine (DB04840)
- Weight
- Average: 175.2303
Monoisotopic: 175.110947431 - Chemical Formula
- C10H13N3
- Synonyms
- Debrisochinum
- Debrisoquin
- Debrisoquina
- Debrisoquine
- Débrisoquine
- Debrisoquinum
Pharmacology
- Indication
For the treatment of moderate and severe hypertension, either alone or as an adjunct, and for the treatment of renal hypertension.
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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
Debrisoquin is an adrenergic neuron-blocking drug similar in effects to guanethidine. It is a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.
- Mechanism of action
Debrisoquin acts at the sympathetic neuroeffector junction by inhibiting or interfering with the release and/or distribution of norepinephrine, rather than acting at the effector cell by inhibiting the association of norepinephrine with its receptors. It is taken up by norepinephrine transporters. It becomes concentrated in NE transmitter vesicles, replacing NE in these vesicles. This leads to a gradual depletion of NE stores in the nerve endings. Once inside the terminal it blocks the release of noradrenaline in response to arrival of an action potential. In contrast to ganglionic blocking agents, debrisoquin suppresses equally the responses mediated by alpha-and beta-adrenergic receptors but does not produce parasympathetic blockade. Since sympathetic blockade results in modest decreases in peripheral resistance and cardiac output, debrisoquin lowers blood pressure in the supine position. It further reduces blood pressure by decreasing the degree of vasoconstriction that normally results from reflex sympathetic nervous activity upon assumption of the upright posture, thus reducing venous return and cardiac output more.
Target Actions Organism ASodium-dependent noradrenaline transporter inducerHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Hepatic.
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- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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 softwareAbaloparatide Abaloparatide may increase the hypotensive activities of Debrisoquine. Abatacept The metabolism of Debrisoquine can be increased when combined with Abatacept. Abiraterone The metabolism of Debrisoquine can be decreased when combined with Abiraterone. Acebutolol The metabolism of Debrisoquine can be decreased when combined with Acebutolol. Aceclofenac The therapeutic efficacy of Debrisoquine can be decreased when used in combination with Aceclofenac. - Food Interactions
- Take with or without food. The absorption is unaffected by food.
Products
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Ingredient UNII CAS InChI Key Debrisoquine sulfate Q94064N9NW 581-88-4 CAYGYVYWRIHZCQ-UHFFFAOYSA-N - International/Other Brands
- Bonipress (lkapharm) / Declinax (Roche) / Tendor (Chinoin)
Categories
- ATC Codes
- C02CC04 — Debrisoquine
- Drug Categories
- Adrenergic Agents
- Antiadrenergic Agents, Peripherally Acting
- Antihypertensive Agents
- Autonomic Agents
- Cardiovascular Agents
- Catecholamines
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 Substrates
- Guanidine Derivatives
- Heterocyclic Compounds, Fused-Ring
- Isoquinolines
- Neurotransmitter Agents
- P-glycoprotein substrates
- Peripheral Nervous System Agents
- Sympatholytics
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as tetrahydroisoquinolines. These are tetrahydrogenated isoquinoline derivatives.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Tetrahydroisoquinolines
- Sub Class
- Not Available
- Direct Parent
- Tetrahydroisoquinolines
- Alternative Parents
- Benzenoids / Guanidines / Carboximidamides / Azacyclic compounds / Organopnictogen compounds / Imines / Hydrocarbon derivatives
- Substituents
- Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carboximidamide / Guanidine / Hydrocarbon derivative / Imine / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- carboxamidine, isoquinolines (CHEBI:34665)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- X31CDK040E
- CAS number
- 1131-64-2
- InChI Key
- JWPGJSVJDAJRLW-UHFFFAOYSA-N
- InChI
- InChI=1S/C10H13N3/c11-10(12)13-6-5-8-3-1-2-4-9(8)7-13/h1-4H,5-7H2,(H3,11,12)
- IUPAC Name
- 1,2,3,4-tetrahydroisoquinoline-2-carboximidamide
- SMILES
- NC(=N)N1CCC2=CC=CC=C2C1
References
- Synthesis Reference
Wenner,W.; U.S. Patent 3,157,573; November 17,1964; assigned to Hoffmann-LaRoche, Inc.
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0006543
- KEGG Compound
- C13650
- PubChem Compound
- 2966
- PubChem Substance
- 46507664
- ChemSpider
- 2860
- BindingDB
- 50122613
- 3118
- ChEBI
- 34665
- ChEMBL
- CHEMBL169901
- ZINC
- ZINC000003594299
- Therapeutic Targets Database
- DAP000125
- PharmGKB
- PA452616
- Wikipedia
- Debrisoquine
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count Not Available Unknown Status Other Healthy Subjects (HS) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 278-280 °C PhysProp logP 0.75 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.842 mg/mL ALOGPS logP 0.58 ALOGPS logP 1.07 Chemaxon logS -2.3 ALOGPS pKa (Strongest Basic) 12.47 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 53.11 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 63.85 m3·mol-1 Chemaxon Polarizability 19.48 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 + 0.9714 Blood Brain Barrier + 0.9106 Caco-2 permeable + 0.5 P-glycoprotein substrate Substrate 0.8427 P-glycoprotein inhibitor I Non-inhibitor 0.8781 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Inhibitor 0.8817 CYP450 2C9 substrate Non-substrate 0.8429 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Non-substrate 0.7101 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.9549 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.9532 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9462 Ames test Non AMES toxic 0.7018 Carcinogenicity Non-carcinogens 0.976 Biodegradation Not ready biodegradable 0.9422 Rat acute toxicity 2.7479 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.6904 hERG inhibition (predictor II) Inhibitor 0.5928
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0ue9-2900000000-5f2dcf1ab6da5e83a08a Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0900000000-5deb90f73bb93308cff7 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-2900000000-aec4221b654ddee5d07f Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0900000000-8219978c5f92fed50beb Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00kf-6900000000-198ab5c9c978861573ca Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-0900000000-33463e1195da20620136 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001l-5900000000-11cf232d32ce02e4ccd0 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 141.5480292 predictedDarkChem Lite v0.1.0 [M-H]- 135.38689 predictedDeepCCS 1.0 (2019) [M+H]+ 143.1160292 predictedDarkChem Lite v0.1.0 [M+H]+ 138.13324 predictedDeepCCS 1.0 (2019) [M+Na]+ 141.6097292 predictedDarkChem Lite v0.1.0 [M+Na]+ 147.29137 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Norepinephrine:sodium symporter activity
- Specific Function
- Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
- Gene Name
- SLC6A2
- Uniprot ID
- P23975
- Uniprot Name
- Sodium-dependent noradrenaline transporter
- Molecular Weight
- 69331.42 Da
References
- Joyce PI, Rizzi D, Calo G, Rowbotham DJ, Lambert DG: The effect of guanethidine and local anesthetics on the electrically stimulated mouse vas deferens. Anesth Analg. 2002 Nov;95(5):1339-43, table of contents. [Article]
- Bryan-Lluka LJ, Seers H, Sharpe I: Amezinium and debrisoquine are substrates of uptake1 and potent inhibitors of monoamine oxidase in perfused lungs of rats. Naunyn Schmiedebergs Arch Pharmacol. 1996 Apr;353(5):536-44. [Article]
- Mitchell JR, Cavanaugh JH, Arias L, Oates JA: Guanethidine and related agents. 3. Antagonism by drugs which inhibit the norepinephrine pump in man. J Clin Invest. 1970 Aug;49(8):1596-604. [Article]
- Yi E, Love JA: Alpha-adrenergic modulation of synaptic transmission in rabbit pancreatic ganglia. Auton Neurosci. 2005 Oct 30;122(1-2):45-57. Epub 2005 Aug 25. [Article]
- Galli A, Blakely RD, DeFelice LJ: Norepinephrine transporters have channel modes of conduction. Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8671-6. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d 24-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Granvil CP, Krausz KW, Gelboin HV, Idle JR, Gonzalez FJ: 4-Hydroxylation of debrisoquine by human CYP1A1 and its inhibition by quinidine and quinine. J Pharmacol Exp Ther. 2002 Jun;301(3):1025-32. doi: 10.1124/jpet.301.3.1025. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Flockhart Table of Drug Interactions [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR: Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999 Mar;16(3):408-14. [Article]
Drug created at September 26, 2007 15:28 / Updated at January 02, 2024 23:51