Zaleplon
Explore a selection of our essential drug information below, or:
Identification
- Summary
Zaleplon is a sedative used for short term treatment of insomnia in adults.
- Brand Names
- Sonata
- Generic Name
- Zaleplon
- DrugBank Accession Number
- DB00962
- Background
Zaleplon is a sedative/hypnotic, mainly used for insomnia. It is known as a nonbenzodiazepine hypnotic. Zaleplon interacts with the GABA receptor complex and shares some of the pharmacological properties of the benzodiazepines. Zaleplon is a schedule IV drug in the United States.
- Type
- Small Molecule
- Groups
- Approved, Illicit, Investigational
- Structure
- Weight
- Average: 305.3339
Monoisotopic: 305.127660127 - Chemical Formula
- C17H15N5O
- Synonyms
- 3'-(3-Cyanopyrazolo(1,5-a)pyrimidin-7-yl)-N-ethylacetanilide
- Zaleplon
- External IDs
- CL 284,846
- CL-284846
- DEA No. 2781
- L846
- LJC 10846
- LJC-10846
- SKP-1041
- ZAL-846
Pharmacology
- Indication
For the treatment of short-term treatment of insomnia in adults.
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 Insomnia •••••••••••• - 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
Zaleplon is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zaleplon is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zaleplon also binds selectively to the CNS GABAA-receptor chloride ionophore complex at benzodiazepine(BZ) omega-1 (BZ1, ο1) receptors.
- Mechanism of action
Zaleplon exerts its action through subunit modulation of the GABABZ receptor chloride channel macromolecular complex. Zaleplon also binds selectively to the brain omega-1 receptor located on the alpha subunit of the GABA-A/chloride ion channel receptor complex and potentiates t-butyl-bicyclophosphorothionate (TBPS) binding.
Target Actions Organism AGamma-aminobutyric acid receptor subunit alpha-1 potentiatorHumans - Absorption
Absorption Zaleplon is rapidly and almost completely absorbed following oral administration.
- Volume of distribution
- 1.4 L/kg
- Protein binding
Approximately 60% (in vitro plasma protein binding).
- Metabolism
Zaleplon is primarily metabolized by aldehyde oxidase.
Hover over products below to view reaction partners
- Route of elimination
Zaleplon is metabolized primarily by the liver and undergoes significant presystemic metabolism. After oral administration, zaleplon is extensively metabolized, with less than 1% of the dose excreted unchanged in urine. Renal excretion of unchanged zaleplon accounts for less than 1% of the administered dose.
- Half-life
Approximately 1 hour
- Clearance
- 1 L/h/kg
- 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
Side effects include abdominal pain, amnesia, dizziness, drowsiness, eye pain, headache, memory loss, menstrual pain, nausea, sleepiness, tingling, weakness
- 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 software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Zaleplon is combined with 1,2-Benzodiazepine. Abacavir Zaleplon may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Zaleplon can be increased when it is combined with Abametapir. Abatacept The metabolism of Zaleplon can be increased when combined with Abatacept. Acalabrutinib The metabolism of Zaleplon can be decreased when combined with Acalabrutinib. - Food Interactions
- Avoid alcohol. Ingesting alcohol may increase the CNS depressant effects of zaleplon.
- Do not take with or immediately after a high-fat meal. The effects of zaleplon are reduced when taken with a high-fat meal.
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 Images
- International/Other Brands
- Zalaplon
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Sonata Capsule 10 mg Oral Meda A.B. 2016-09-08 2015-07-03 EU Sonata Capsule 5 mg Oral Meda A.B. 2016-09-08 2015-07-03 EU Sonata Capsule 10 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 1999-08-13 2019-05-31 US Sonata Capsule 10 mg Oral Meda A.B. 2016-09-08 2015-07-03 EU Sonata Capsule 10 mg/1 Oral Physicians Total Care, Inc. 2004-04-01 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Zaleplon Capsule 10 mg/1 Oral Physicians Total Care, Inc. 2008-06-19 Not applicable US Zaleplon Capsule 10 mg/1 Oral Hikma Pharmaceuticals USA Inc. 2008-12-01 2010-12-01 US Zaleplon Capsule 10 mg/1 Oral Unichem Pharmaceuticals (USA), Inc. 2009-05-05 Not applicable US Zaleplon Capsule 5 mg/1 Oral Rebel Distributors 2009-05-05 Not applicable US Zaleplon Capsule 10 mg/1 Oral A-S Medication Solutions 2008-06-06 2017-11-21 US
Categories
- ATC Codes
- N05CF03 — Zaleplon
- Drug Categories
- Acetates
- Acids, Acyclic
- Amides
- Anticonvulsants
- Benzodiazepine hypnotics and sedatives
- Central Nervous System Agents
- Central Nervous System Depressants
- Central Nervous System Depression
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- GABA Agents
- GABA Agonists
- GABA Modulators
- GABA-A Receptor Agonists
- gamma-Aminobutyric Acid A Receptor Agonist
- Hypnotics (Nonbenzodiazepine)
- Hypnotics and Sedatives
- Miscellaneous Anxiolytics Sedatives and Hypnotics
- Nervous System
- Neurotransmitter Agents
- Psycholeptics
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazines
- Sub Class
- Pyrimidines and pyrimidine derivatives
- Direct Parent
- Phenylpyrimidines
- Alternative Parents
- Acetanilides / Pyrazolo[1,5-a]pyrimidines / Tertiary carboxylic acid amides / Pyrazoles / Heteroaromatic compounds / Acetamides / Nitriles / Azacyclic compounds / Organopnictogen compounds / Organic oxides show 2 more
- Substituents
- 4-phenylpyrimidine / 5-phenylpyrimidine / Acetamide / Acetanilide / Anilide / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Carbonitrile show 17 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- nitrile, pyrazolopyrimidine (CHEBI:10102)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- S62U433RMH
- CAS number
- 151319-34-5
- InChI Key
- HUNXMJYCHXQEGX-UHFFFAOYSA-N
- InChI
- InChI=1S/C17H15N5O/c1-3-21(12(2)23)15-6-4-5-13(9-15)16-7-8-19-17-14(10-18)11-20-22(16)17/h4-9,11H,3H2,1-2H3
- IUPAC Name
- N-(3-{3-cyanopyrazolo[1,5-a]pyrimidin-7-yl}phenyl)-N-ethylacetamide
- SMILES
- CCN(C(C)=O)C1=CC=CC(=C1)C1=CC=NC2=C(C=NN12)C#N
References
- Synthesis Reference
Farhan Aslam, "Polymorphs of zaleplon and methods for the preparation thereof." U.S. Patent US20020072527, issued June 13, 2002.
US20020072527- General References
- Dundar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T: Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Hum Psychopharmacol. 2004 Jul;19(5):305-22. [Article]
- Noguchi H, Kitazumi K, Mori M, Shiba T: Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. J Pharmacol Sci. 2004 Mar;94(3):246-51. [Article]
- Ramakrishnan K, Scheid DC: Treatment options for insomnia. Am Fam Physician. 2007 Aug 15;76(4):517-26. [Article]
- Barbera J, Shapiro C: Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf. 2005;28(4):301-18. [Article]
- Dooley M, Plosker GL: Zaleplon: a review of its use in the treatment of insomnia. Drugs. 2000 Aug;60(2):413-45. [Article]
- Holm KJ, Goa KL: Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Drugs. 2000 Apr;59(4):865-89. [Article]
- Patat A, Paty I, Hindmarch I: Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent. Hum Psychopharmacol. 2001 Jul;16(5):369-392. [Article]
- External Links
- Human Metabolome Database
- HMDB0015097
- KEGG Drug
- D00530
- KEGG Compound
- C07484
- PubChem Compound
- 5719
- PubChem Substance
- 46508267
- ChemSpider
- 5517
- BindingDB
- 86521
- 74667
- ChEBI
- 10102
- ChEMBL
- CHEMBL1521
- ZINC
- ZINC000000006300
- Therapeutic Targets Database
- DAP000266
- PharmGKB
- PA451952
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Zaleplon
- FDA label
- Download (66.1 KB)
- MSDS
- Download (57.6 KB)
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 Completed Not Available Sleep 1 somestatus stop reason just information to hide Not Available Completed Treatment Short Term Treatment of Insomnia 2 somestatus stop reason just information to hide 4 Completed Basic Science Memory / Sleep 1 somestatus stop reason just information to hide 4 Completed Supportive Care Cognitive Functioning / Pharmacologic Actions / Sleep 1 somestatus stop reason just information to hide 3 Terminated Treatment Anxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- King pharmaceuticals research and development inc sub king pharmaceuticals inc
- Aurobindo pharma ltd
- Cipla ltd
- Mylan pharmaceuticals inc
- Orchid healthcare div orchid chemicals and pharmaceuticals ltd
- Roxane laboratories inc
- Sandoz inc
- Teva pharmaceuticals usa
- Unichem laboratories ltd
- Upsher smith laboratories inc
- West ward pharmaceutical corp
- Packagers
- A-S Medication Solutions LLC
- Aurobindo Pharma Ltd.
- Cipla Ltd.
- Corepharma LLC
- DAVA Pharmaceuticals
- DispenseXpress Inc.
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Greenstone LLC
- Innoviant Pharmacy Inc.
- King Pharmaceuticals Inc.
- Mylan
- Northstar Rx LLC
- Nucare Pharmaceuticals Inc.
- Physicians Total Care Inc.
- Rebel Distributors Corp.
- Roxane Labs
- Teva Pharmaceutical Industries Ltd.
- Unichem Laboratories Ltd.
- USL Pharma Inc.
- West-Ward Pharmaceuticals
- Dosage Forms
Form Route Strength Capsule Oral Capsule, coated Oral 5 mg Capsule Oral 10 mg Capsule Oral 5 mg Capsule Oral 10 mg/1 Capsule Oral 5 mg/1 Capsule, gelatin coated Oral 10 mg/1 Capsule, gelatin coated Oral 5 mg/1 - Prices
Unit description Cost Unit Sonata 10 mg capsule 6.83USD capsule Sonata 5 mg capsule 5.26USD capsule Zaleplon 5 mg capsule 2.13USD capsule Zaleplon 10 mg capsule 2.09USD 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) 157-159 °C Not Available logP 0.9 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0403 mg/mL ALOGPS logP 2 ALOGPS logP 1.53 Chemaxon logS -3.9 ALOGPS pKa (Strongest Basic) 0.28 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 74.29 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 97.24 m3·mol-1 Chemaxon Polarizability 32.09 Å3 Chemaxon Number of Rings 3 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 + 1.0 Blood Brain Barrier + 0.9751 Caco-2 permeable + 0.5973 P-glycoprotein substrate Non-substrate 0.6094 P-glycoprotein inhibitor I Non-inhibitor 0.5232 P-glycoprotein inhibitor II Inhibitor 0.8239 Renal organic cation transporter Non-inhibitor 0.745 CYP450 2C9 substrate Non-substrate 0.8607 CYP450 2D6 substrate Non-substrate 0.8551 CYP450 3A4 substrate Substrate 0.6341 CYP450 1A2 substrate Non-inhibitor 0.5 CYP450 2C9 inhibitor Inhibitor 0.5986 CYP450 2D6 inhibitor Non-inhibitor 0.9507 CYP450 2C19 inhibitor Non-inhibitor 0.5238 CYP450 3A4 inhibitor Non-inhibitor 0.8396 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7673 Ames test Non AMES toxic 0.5372 Carcinogenicity Non-carcinogens 0.6481 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.6277 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9806 hERG inhibition (predictor II) Non-inhibitor 0.8931
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 190.4219393 predictedDarkChem Lite v0.1.0 [M-H]- 189.3782393 predictedDarkChem Lite v0.1.0 [M-H]- 165.6831 predictedDeepCCS 1.0 (2019) [M+H]+ 190.7502393 predictedDarkChem Lite v0.1.0 [M+H]+ 190.7896393 predictedDarkChem Lite v0.1.0 [M+H]+ 168.0411 predictedDeepCCS 1.0 (2019) [M+Na]+ 190.7797393 predictedDarkChem Lite v0.1.0 [M+Na]+ 190.1029393 predictedDarkChem Lite v0.1.0 [M+Na]+ 174.82384 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Potentiator
- General Function
- Alpha subunit of the heteropentameric ligand-gated chloride channel gated by Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:23909897, PubMed:25489750, PubMed:29950725, PubMed:30602789). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (PubMed:29950725, PubMed:30602789). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:23909897, PubMed:29950725, PubMed:30602789). Alpha-1/GABRA1-containing GABAARs are largely synaptic (By similarity). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:23909897, PubMed:25489750). GABAARs function also as histamine receptor where histamine binds at the interface of two neighboring beta subunits and potentiates GABA response (By similarity). GABAARs containing alpha, beta and epsilon subunits also permit spontaneous chloride channel activity while preserving the structural information required for GABA-gated openings (By similarity). Alpha-1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection (By similarity). Together with rho subunits, may also control neuronal and glial GABAergic transmission in the cerebellum (By similarity)
- Specific Function
- GABA-A receptor activity
- Gene Name
- GABRA1
- Uniprot ID
- P14867
- Uniprot Name
- Gamma-aminobutyric acid receptor subunit alpha-1
- Molecular Weight
- 51801.395 Da
References
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
- Patat A, Paty I, Hindmarch I: Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent. Hum Psychopharmacol. 2001 Jul;16(5):369-392. [Article]
- Barbera J, Shapiro C: Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf. 2005;28(4):301-18. [Article]
- Sanger DJ, Griebel G, Perrault G, Claustre Y, Schoemaker H: Discriminative stimulus effects of drugs acting at GABA(A) receptors: differential profiles and receptor selectivity. Pharmacol Biochem Behav. 1999 Oct;64(2):269-73. [Article]
- Terzano MG, Rossi M, Palomba V, Smerieri A, Parrino L: New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon. Drug Saf. 2003;26(4):261-82. [Article]
Enzymes
- 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
- Tanoue C, Sugihara K, Uramaru N, Tayama Y, Watanabe Y, Horie T, Ohta S, Kitamura S: Prediction of human metabolism of the sedative-hypnotic zaleplon using chimeric mice transplanted with human hepatocytes. Xenobiotica. 2013 Nov;43(11):956-62. doi: 10.3109/00498254.2013.788232. Epub 2013 May 8. [Article]
- Renwick AB, Mistry H, Ball SE, Walters DG, Kao J, Lake BG: Metabolism of Zaleplon by human hepatic microsomal cytochrome P450 isoforms. Xenobiotica. 1998 Apr;28(4):337-48. doi: 10.1080/004982598239452 . [Article]
- Foye, William O.;Williams, David A.;Lemke, Thomas L. (2002). Foye's Principles of Medicinal Chemistry (5th ed.). Lippincott Williams & Wilkins. [ISBN:0683307371]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). 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:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion 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 all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). 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:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
- Specific Function
- all-trans retinoic acid 18-hydroxylase activity
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57469.95 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide, N-methylphthalazinium and phthalazine, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. May also catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis
- Specific Function
- 2 iron, 2 sulfur cluster binding
- Gene Name
- AOX1
- Uniprot ID
- Q06278
- Uniprot Name
- Aldehyde oxidase
- Molecular Weight
- 147916.735 Da
References
- Lake BG, Ball SE, Kao J, Renwick AB, Price RJ, Scatina JA: Metabolism of zaleplon by human liver: evidence for involvement of aldehyde oxidase. Xenobiotica. 2002 Oct;32(10):835-47. [Article]
- Obach RS: Potent inhibition of human liver aldehyde oxidase by raloxifene. Drug Metab Dispos. 2004 Jan;32(1):89-97. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 29, 2024 14:47