DEBRISOQUIN SULFATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	2C10H13N3.H2O4S
Molecular Weight	448.539
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(O)(=O)=O.NC(=N)N1CCC2=CC=CC=C2C1.NC(=N)N3CCC4=CC=CC=C4C3

InChI

InChIKey=CAYGYVYWRIHZCQ-UHFFFAOYSA-N

InChI=1S/2C10H13N3.H2O4S/c2*11-10(12)13-6-5-8-3-1-2-4-9(8)7-13;1-5(2,3)4/h2*1-4H,5-7H2,(H3,11,12);(H2,1,2,3,4)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2601584 | https://www.ncbi.nlm.nih.gov/pubmed/8471132 | https://www.ncbi.nlm.nih.gov/pubmed/19102711

Debrisoquin is an antihypertensive drug having guanethidine-like properties, which inhibits monoamine oxidase (MAO) and does not enter the brain. Debrisoquine was used for the treatment of hypertension. Debrisoquine hydroxylation phenotype has been the most used test in humans to evaluate CYP2D6 activity. Two debrisoquine hydroxylation phenotypes have been described: poor and extensive metabolizers. A group with a very low debrisoquine metabolic ratio within the extensive metabolizers, named ultrarapid metabolizers, has also been distinguished. This CYP2D6 variability can be for a large part alternatively determined by genotyping, which appears to be of clinical importance given CYP2D6 involvement in the metabolism of a large number of commonly prescribed drugs.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cytochrome P450 2D6 61 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8911874 \| https://www.ncbi.nlm.nih.gov/pubmed/17273835 \| https://www.ncbi.nlm.nih.gov/pubmed/19102711	Substrate 661
Monoamine oxidase A 49 Target ID: CHEMBL1951 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2601584	Inhibitor 8297	0.5 µM [IC50]
Monoamine oxidase B 72 Target ID: CHEMBL2039 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2601584	Inhibitor 8297	8.8 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://www.ncbi.nlm.nih.gov/pubmed/5296799 http://dtb.bmj.com/content/5/11/44 https://www.ncbi.nlm.nih.gov/pubmed/14286208 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/575083?redirect=true	Primary		Approved 8429	DECLINAX Approved Use Hypertension

PubMed

Title	Date	PubMed
Factors predisposing to postural hypotensive symptoms in the treatment of high blood pressure.	1975 Oct	127594
Is cytochrome P450 CYP2D activity present in pig liver?	2002 Oct	12530471
Alteration in catalytic properties of human CYP2D6 caused by substitution of glycine-42 with arginine, lysine and glutamic acid.	2003	15618721
Cytochrome P450 in vitro reaction phenotyping: a re-evaluation of approaches used for P450 isoform identification.	2003 Apr	12642457
The relative contribution of monoamine oxidase and cytochrome p450 isozymes to the metabolic deamination of the trace amine tryptamine.	2003 Feb	12538805
Disposition of debrisoquine and nortriptyline in Korean subjects in relation to CYP2D6 genotypes, and comparison with Caucasians.	2003 Jun	12814461
The Karolinska cocktail for phenotyping of five human cytochrome P450 enzymes.	2003 Jun	12811361
Stereoselective metabolism of metoprolol: enantioselectivity of alpha-hydroxymetoprolol in plasma and urine.	2003 Jun	12774293
Effect of hepatic impairment on the pharmacokinetics of atomoxetine and its metabolites.	2003 Mar	12621383
Interaction of serum proteins with CYP isoforms in human liver microsomes: inhibitory effects of human and bovine albumin, alpha-globulins, alpha-1-acid glycoproteins and gamma-globulins on CYP2C19 and CYP2D6.	2003 Mar 14	12597994
Quinine 3-hydroxylation as a biomarker reaction for the activity of CYP3A4 in man.	2003 May	12743670
Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype.	2003 May	12682803
Cytochrome P450 expression and testosterone metabolism in the liver of deer.	2003 May 1	12679052
The hepatic and intestinal metabolic activities of P450 in rats with surgery- and drug-induced renal dysfunction.	2003 Oct	14620512
Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes.	2003 Oct	12968986
CSF taurine level is influenced by plasma cholesterol and the CYP2D6 phenotype.	2003 Oct	12957331
Polymorphisms in the CYP1B1 gene are associated with increased risk of prostate cancer.	2003 Oct 20	14562027
Interferon-beta treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity.	2003 Sep	12919185
Effect of ketoconazole on venlafaxine plasma concentrations in extensive and poor metabolisers of debrisoquine.	2003 Sep	12898080
CYP1A1 and CYP2D6 polymorphism and risk of lung cancer in a North Indian population.	2003 Sep-Oct	14602525
Rapid determination of five probe drugs and their metabolites in human plasma and urine by liquid chromatography/tandem mass spectrometry: application to cytochrome P450 phenotyping studies.	2004	15529418
Altered distribution of the debrisoquine oxidative phenotypes in children with type 1 diabetes mellitus.	2004	14726620
Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1.	2004 Apr	15499174
The role of cytochrome P450 enzymes in the metabolism of risperidone and its clinical relevance for drug interactions.	2004 Aug	15270204
Genetics in melanoma.	2004 Dec	15609895
Bioequivalence revisited: influence of age and sex on CYP enzymes.	2004 Dec	15592333
Assessment of in vivo CYP2D6 activity: differential sensitivity of commonly used probes to urine pH.	2004 Dec	15545311
Influence of phenylalanine 120 on cytochrome P450 2D6 catalytic selectivity and regiospecificity: crucial role in 7-methoxy-4-(aminomethyl)-coumarin metabolism.	2004 Dec 1	15498516
Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.	2004 Feb	14748815
Genetic polymorphisms of hormone-related genes and prostate cancer risk in the Japanese population.	2004 Jul-Aug	15330195
Assessment of drug-drug interaction potential of enfuvirtide in human immunodeficiency virus type 1-infected patients.	2004 Jun	15179410
Relationship between Type A and B personality and debrisoquine hydroxylation capacity.	2004 Jun	15151524
Relationship between haloperidol plasma concentration, debrisoquine metabolic ratio, CYP2D6 and CYP2C9 genotypes in psychiatric patients.	2004 Mar	15048614
Polymorphic cytochrome P450 2D6: humanized mouse model and endogenous substrates.	2004 May	15237854
In vivo assessment of botanical supplementation on human cytochrome P450 phenotypes: Citrus aurantium, Echinacea purpurea, milk thistle, and saw palmetto.	2004 Nov	15536458
The roles of amino acid residues at positions 43 and 45 in microsomal contents and enzymatic functions of rat CYP2D1 and CYP2D2.	2004 Nov 12	15474473
[Assessment of CYP2D6 activity as a form of optimizing antidepressant therapy].	2004 Nov-Dec	15779673
[CYP 2D6 activity profile among patients with depression].	2004 Nov-Dec	15779672
A case report of a poor metabolizer of CYP2D6 presented with unusual responses to nortriptyline medication.	2004 Oct	15483356
Fatal intoxication cases: cytochrome P450 2D6 and 2C19 genotype distributions.	2004 Oct	15349706
Determination of cytochrome P450 2D6 (CYP2D6) gene copy number by real-time quantitative PCR.	2005	16192683
The AGNP-TDM Expert Group Consensus Guidelines: focus on therapeutic monitoring of antidepressants.	2005	16156382
Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and Ginkgo biloba.	2005	15974642
Determination of debrisoquine and 4-hydroxydebrisoquine by high-performance liquid chromatography: application to the evaluation of CYP2D6 genotype and debrisoquine metabolic ratio relationship.	2005	15843230
Influence of chronic renal failure on stereoselective metoprolol metabolism in hypertensive patients.	2005 Dec	16291718
Effect of age and postoperative time on cytochrome p450 enzyme activity following liver transplantation.	2005 Jun	15901748
In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes.	2005 May	15900287
Functional analysis of CYP2D6.31 variant: homology modeling suggests possible disruption of redox partner interaction by Arg440His substitution.	2005 May 1	15726636
Metabolism of N-hydroxyguanidines (N-hydroxydebrisoquine) in human and porcine hepatocytes: reduction and formation of glucuronides.	2005 Oct	16033947
Cytochrome P450 mRNA expression in peripheral blood lymphocytes as a predictor of enzyme induction.	2005 Sep	16041547

Patents

Sample Use Guides

In Vivo Use Guide

Adult: 10-20 mg once-bid, increased by 10-20 mg every 3 or 4 days according to severity of condition. Maintenance: 20-120 mg daily. Max Dosage: ≥300 mg daily. More: https://www.ndrugs.com/?s=declinax

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

DEBRISOQUIN SULFATE

Official Name

English

2(1H)-ISOQUINOLINECARBOXIMIDAMIDE, 3,4-DIHYDRO-, SULFATE (2:1)

Systematic Name

English

3,4-Dihydro-2(1H)-isoquinolinecarboxamidine sulfate (2:1)

Systematic Name

English

3,4-DIHYDRO-2(1H)-ISOQUINOLINECARBOXAMIDINE SULPHATE (2:1)

Systematic Name

English

DEBRISOQUINE SULFATE [MART.]

Common Name

English

DEBRISOQUIN SULPHATE

Common Name

English

DEBRISOQUIN SULFATE [USAN]

Common Name

English

NSC-139330

Code

English

Debrisoquine sulfate [WHO-DD]

Common Name

English

RO 5-3307/1

Code

English

DEBRISOQUINE SULFATE

Common Name

English

RO-5-3307/1

Code

English

DEBRISOQUIN SULFATE [MI]

Common Name

English

2(1H)-ISOQUINOLINECARBOXIMIDAMIDE, 3,4-DIHYDRO-, SULPHATE (2:1)

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29713