Explore a selection of our essential drug information below, or:
Identification
- Summary
Manidipine is a dihydropyridine calcium channel blocker used to treat hypertension.
- Generic Name
- Manidipine
- DrugBank Accession Number
- DB09238
- Background
Manidipine (INN) is a calcium channel blocker (dihydropyridine type) that is used clinically as an antihypertensive. It is selective for vasculature and does not produce effects on the heart at clinically relevant dosages.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Manidipine (DB09238)
- Weight
- Average: 610.711
Monoisotopic: 610.27913496 - Chemical Formula
- C35H38N4O6
- Synonyms
- Manidipine
- Manidipino
Pharmacology
- Indication
For the treatment of hypertension.
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 Treatment of Mild to moderate hypertension •••••••••••• •••••• - 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
Manidipine produces vasodilation resulting in lower blood pressure 1.
- Mechanism of action
Contraction of vascular smooth muscle is stimulated by Gq coupled receptors which produce calcium release from the sarcoplasmic reticulum. This is followed by opening of voltage dependent calcium channels and an influx of calcium into the cell ultimately producing contraction. Manidipine binds to and dissociates slowly from L- and T-type voltage dependent calcium channels on smooth muscle cells, blocking the entrance of extracellular calcium into the cell and preventing this contraction 1,2. This produces vasodilation which decreases blood pressure. Manidipine produces renal vasodilation and an increase in natriuresis. This likely contributes to the antihypertensive effect by reducing blood volume. Manidipine is selective for the vasculature and does not produce significant effects on the heart or central nervous system at clinically relevant dosages.
Target Actions Organism AVoltage-dependent L-type calcium channel blockerHumans AVoltage-dependent L-type calcium channel subunit alpha-1C inhibitorHumans ACruzipain inhibitorTrypanosoma cruzi AVoltage-dependent L-type calcium channel subunit alpha-1D inhibitorHumans AVoltage-dependent T-type calcium channel inhibitorblockerHumans UVoltage-dependent T-type calcium channel subunit alpha-1G inhibitorHumans UVoltage-dependent T-type calcium channel subunit alpha-1H inhibitorHumans UVoltage-dependent T-type calcium channel subunit alpha-1I inhibitorHumans - Absorption
The median Tmax is 1.5 h 1. Administration with food produces an 1.3-1.6-fold increase in Cmax but no change in Tmax. Manidipine does not accumulate significantly with multiple doses.
- Volume of distribution
Not Available
- Protein binding
Manidipine is 99% bound to human plasma proteins 1.
- Metabolism
Manidipine is extensively metabolized by CYP enzymes to pyridine derivatives and diphenylmethane derivatives which make up 4-7% and 22-24% of the dose excreted in the urine 1.
- Route of elimination
Manidipine is eliminated through extensive metabolism. 63% is eliminated in the feces and 31% in the urine as metabolites 1.
- Half-life
The half life of elimination has been observed to be dose dependent 1. Doses of 5, 10, and 20 mg produced half lives of 3.94, 5.02, and 7.95 h respectively.
- 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
The most common adverse events reported in clinical trials were ankle oedema (6%), headache (3.8%), palpitation (2.7%), flushing (2.2%), dizziness (1.6%), rash (0.5%) and fatigue (0.5%) 1.
- Pathways
- Not Available
- 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 softwareAbaloparatide Abaloparatide may increase the hypotensive activities of Manidipine. Abametapir The serum concentration of Manidipine can be increased when it is combined with Abametapir. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Manidipine. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Manidipine. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Manidipine. - Food Interactions
- Not Available
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 Manidipine dihydrochloride ZL507UZ6QL 89226-75-5 JINNGBXKBDUGQT-UHFFFAOYSA-N - International/Other Brands
- Manyper
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image FRAGOR Manidipine (10 MG) + Delapril (30 MG) Tablet Oral Chiesi Farmaceutici S.P.A. 2014-07-08 2021-06-01 Italy 
FRAGOR Manidipine (10 MG) + Delapril (30 MG) Tablet Oral Chiesi Farmaceutici S.P.A. 2014-07-08 2021-04-04 Italy FRAGOR Manidipine (10 MG) + Delapril (30 MG) Tablet Oral Chiesi Farmaceutici S.P.A. 2014-07-08 2021-04-04 Italy FRAGOR Manidipine (10 MG) + Delapril (30 MG) Tablet Oral Chiesi Farmaceutici S.P.A. 2014-07-08 2021-04-04 Italy VIVACE 30/10MG TABLETTEN Manidipine dihydrochloride (10 mg) + Delapril hydrochloride (30 mg) Tablet Oral 2016-07-01 Not applicable Germany 
Categories
- ATC Codes
- C08CA11 — Manidipine
- C08CA — Dihydropyridine derivatives
- C08C — SELECTIVE CALCIUM CHANNEL BLOCKERS WITH MAINLY VASCULAR EFFECTS
- C08 — CALCIUM CHANNEL BLOCKERS
- C — CARDIOVASCULAR SYSTEM
- Drug Categories
- ACE Inhibitors and Calcium Channel Blockers
- Agents causing hyperkalemia
- Antiarrhythmic agents
- Antihypertensive Agents
- Benzene Derivatives
- Bradycardia-Causing Agents
- Calcium Channel Blockers
- Calcium-Regulating Hormones and Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (weak)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (moderate)
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dihydropyridine Derivatives
- Membrane Transport Modulators
- Nitro Compounds
- Pyridines
- Selective Calcium Channel Blockers With Mainly Vascular Effects
- Vasodilating Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Diphenylmethanes
- Direct Parent
- Diphenylmethanes
- Alternative Parents
- Dihydropyridinecarboxylic acids and derivatives / Nitrobenzenes / Nitroaromatic compounds / Aralkylamines / N-alkylpiperazines / Dicarboxylic acids and derivatives / Vinylogous amides / Enoate esters / Methyl esters / Amino acids and derivatives show 11 more
- Substituents
- 1,4-diazinane / Allyl-type 1,3-dipolar organic compound / Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid or derivatives / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / C-nitro compound / Carbonyl group show 32 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 6O4754US88
- CAS number
- 89226-50-6
- InChI Key
- ANEBWFXPVPTEET-UHFFFAOYSA-N
- InChI
- InChI=1S/C35H38N4O6/c1-24-30(34(40)44-3)32(28-15-10-16-29(23-28)39(42)43)31(25(2)36-24)35(41)45-22-21-37-17-19-38(20-18-37)33(26-11-6-4-7-12-26)27-13-8-5-9-14-27/h4-16,23,32-33,36H,17-22H2,1-3H3
- IUPAC Name
- 3-{2-[4-(diphenylmethyl)piperazin-1-yl]ethyl} 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
- SMILES
- COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)N(=O)=O)C(=O)OCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=CC=C1
References
- General References
- External Links
- PubChem Compound
- 4008
- PubChem Substance
- 347827830
- ChemSpider
- 3868
- 29275
- ChEBI
- 135849
- ChEMBL
- CHEMBL1085699
- Wikipedia
- Manidipine
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 data4 Completed Treatment Cardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension, Essential Hypertension / Stroke 1 somestatus stop reason just information to hide 4 Terminated Treatment Hypertension 1 somestatus stop reason just information to hide 3 Completed Diagnostic Type 2 Diabetes Mellitus 1 somestatus stop reason just information to hide 3 Completed Treatment Hypertension 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral Tablet Oral Tablet Oral 20 mg Tablet Oral 10 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility <1mg/mL MSDS - Predicted Properties
Property Value Source Water Solubility 0.000995 mg/mL ALOGPS logP 5.11 ALOGPS logP 5.19 Chemaxon logS -5.8 ALOGPS pKa (Strongest Acidic) 19.47 Chemaxon pKa (Strongest Basic) 7.89 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 116.93 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 175.13 m3·mol-1 Chemaxon Polarizability 65.72 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 228.01349 predictedDeepCCS 1.0 (2019) [M+H]+ 229.8384 predictedDeepCCS 1.0 (2019) [M+Na]+ 235.56187 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 group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Blocker
- General Function
- Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:11741969, PubMed:12176756, PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17071743, PubMed:17224476, PubMed:20953164, PubMed:23677916, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:29078335, PubMed:29742403, PubMed:30023270, PubMed:30172029, PubMed:34163037, PubMed:7737988, PubMed:8099908, PubMed:8392192, PubMed:9013606, PubMed:9087614, PubMed:9607315). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable)
- Specific Function
- Alpha-actinin binding
Components:
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:11741969, PubMed:12176756, PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17071743, PubMed:17224476, PubMed:20953164, PubMed:23677916, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:29078335, PubMed:29742403, PubMed:30023270, PubMed:30172029, PubMed:34163037, PubMed:7737988, PubMed:8099908, PubMed:8392192, PubMed:9013606, PubMed:9087614, PubMed:9607315). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable)
- Specific Function
- Alpha-actinin binding
- Gene Name
- CACNA1C
- Uniprot ID
- Q13936
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1C
- Molecular Weight
- 248974.1 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Trypanosoma cruzi
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Cysteine-type endopeptidase activity
- Specific Function
- Hydrolyzes chromogenic peptides at the carboxyl Arg or Lys; requires at least one more amino acid, preferably Arg, Phe, Val or Leu, between the terminal Arg or Lys and the amino-blocking group.The ...
- Gene Name
- Not Available
- Uniprot ID
- P25779
- Uniprot Name
- Cruzipain
- Molecular Weight
- 49835.59 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines
- Specific Function
- Alpha-actinin binding
- Gene Name
- CACNA1D
- Uniprot ID
- Q01668
- Uniprot Name
- Voltage-dependent L-type calcium channel subunit alpha-1D
- Molecular Weight
- 245138.75 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- InhibitorBlocker
- General Function
- Scaffold protein binding
- Specific Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Components:
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Scaffold protein binding
- Specific Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
- Gene Name
- CACNA1G
- Uniprot ID
- O43497
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1G
- Molecular Weight
- 262468.62 Da
References
- Furukawa T, Nukada T, Namiki Y, Miyashita Y, Hatsuno K, Ueno Y, Yamakawa T, Isshiki T: Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I))) expressed in Xenopus oocytes. Eur J Pharmacol. 2009 Jun 24;613(1-3):100-7. doi: 10.1016/j.ejphar.2009.04.036. Epub 2009 May 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-sensitive calcium channel that gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group. A particularity of this type of channel is an opening at quite negative potentials, and a voltage-dependent inactivation (PubMed:27149520, PubMed:9670923, PubMed:9930755). T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle (Probable). They may also be involved in the modulation of firing patterns of neurons (PubMed:15048902). In the adrenal zona glomerulosa, participates in the signaling pathway leading to aldosterone production in response to either AGT/angiotensin II, or hyperkalemia (PubMed:25907736, PubMed:27729216)
- Specific Function
- High voltage-gated calcium channel activity
- Gene Name
- CACNA1H
- Uniprot ID
- O95180
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1H
- Molecular Weight
- 259160.2 Da
References
- Furukawa T, Nukada T, Namiki Y, Miyashita Y, Hatsuno K, Ueno Y, Yamakawa T, Isshiki T: Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I))) expressed in Xenopus oocytes. Eur J Pharmacol. 2009 Jun 24;613(1-3):100-7. doi: 10.1016/j.ejphar.2009.04.036. Epub 2009 May 3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This channel gives rise to T-type calcium currents. T-type calcium channels belong to the 'low-voltage activated (LVA)' group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H (By similarity)
- Specific Function
- High voltage-gated calcium channel activity
- Gene Name
- CACNA1I
- Uniprot ID
- Q9P0X4
- Uniprot Name
- Voltage-dependent T-type calcium channel subunit alpha-1I
- Molecular Weight
- 245100.8 Da
References
- Furukawa T, Nukada T, Namiki Y, Miyashita Y, Hatsuno K, Ueno Y, Yamakawa T, Isshiki T: Five different profiles of dihydropyridines in blocking T-type Ca(2+) channel subtypes (Ca(v)3.1 (alpha(1G)), Ca(v)3.2 (alpha(1H)), and Ca(v)3.3 (alpha(1I))) expressed in Xenopus oocytes. Eur J Pharmacol. 2009 Jun 24;613(1-3):100-7. doi: 10.1016/j.ejphar.2009.04.036. Epub 2009 May 3. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Unknown if inhibition is clinically relevant.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). 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:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Unknown if inhibition is clinically relevant.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, 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) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:14559847, PubMed:15041462, PubMed:15805301, PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. 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 C15-alpha and C16-alpha positions (PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15805301). Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (PubMed:15041462, PubMed:18577768). Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:15041462, PubMed:19965576, PubMed:20972997). Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system (PubMed:20972997). Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer (PubMed:15041462). May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. 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). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195)
- Specific Function
- Arachidonic acid monooxygenase activity
- Gene Name
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). 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 epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- Anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [Article]
- Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
- McKeage K, Scott LJ: Manidipine: a review of its use in the management of hypertension. Drugs. 2004;64(17):1923-40. [Article]
Drug created at October 23, 2015 16:51 / Updated at August 26, 2024 19:22