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Identification
- Summary
Orphenadrine is a muscarinic antagonist used as an adjunct for the symptomatic relief of musculoskeletal pain and discomfort.
- Brand Names
- Norgesic, Norgesic Forte, Orfenace, Orphengesic
- Generic Name
- Orphenadrine
- DrugBank Accession Number
- DB01173
- Background
A muscarinic antagonist used to treat drug-induced parkinsonism and to relieve pain from muscle spasm.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Orphenadrine (DB01173)
- Weight
- Average: 269.3813
Monoisotopic: 269.177964363 - Chemical Formula
- C18H23NO
- Synonyms
- 2-(phenyl-o-tolylmethoxy)ethyldimethylamine
- 2-methyldiphenhydramine
- beta-Dimethylaminoethyl 2-methylbenzhydryl ether
- Dimethyl-[2-(phenyl-o-tolyl-methoxy)-ethyl]-amine
- N,N-Dimethyl-2-(alpha-2-tolylbenzoyloxy)ethylamine
- N,N-dimethyl-2-(phenyl(o-tolyl)methoxy)ethanamine
- N,N-dimethyl-2-[(o-methyl-α-phenylbenzyl)oxy]ethylamine
- o-methyldiphenhydramine
- o-monomethyldiphenhydramine
- Orfenadrina
- Orphenadrine
- Orphenadrinum
- phenyl-o-tolylmethyl dimethyaminoethyl ether
- β-dimethylaminoethyl 2-methylbenzhydryl ether
Pharmacology
- Indication
Indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculo skeletal conditions.
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 Used in combination to treat Back pain lower back Combination Product in combination with: Ibuprofen (DB01050) •••••••••••• Used in combination to treat Fever Combination Product in combination with: Mefenamic acid (DB00784) •••••••••••• ••••••• •••••• Used in combination to treat Menstrual cramps Combination Product in combination with: Mefenamic acid (DB00784) •••••••••••• ••••••• •••••• Used in combination to treat Mild pain Combination Product in combination with: Mefenamic acid (DB00784) •••••••••••• ••••••• •••••• Treatment of Muscle spasm •••••••••••• - 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
Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anaesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favourable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. The effect is somewhat less on bradykinesia.
- Mechanism of action
Orphenadrine binds and inhibits both histamine H1 receptors and NMDA receptors. It restores the motor disturbances induced by neuroleptics, in particular the hyperkinesia. The dopamine deficiency in the striatum increases the stimulating effects of the cholinergic system. This stimulation is counteracted by the anticholinergic effect of orphenadrine. It may have a relaxing effect on skeletal muscle spasms and it has a mood elevating effect.
Target Actions Organism AGlutamate receptor ionotropic, NMDA 2D antagonistHumans AGlutamate receptor ionotropic, NMDA 1 antagonistHumans AGlutamate receptor ionotropic, NMDA 3B antagonistHumans AGlutamate receptor ionotropic, NMDA 3A antagonistHumans AHistamine H1 receptor antagonistHumans ASodium-dependent noradrenaline transporter inhibitorHumans USodium channel protein type 10 subunit alpha inhibitorHumans - Absorption
Orphenadrine is almost completely absorbed in the gastrointestinal tract.
- Volume of distribution
Not Available
- Protein binding
95%
- Metabolism
Biotransformation occurs mainly in the liver. Pharmacologically active metabolites are N-demethyl orphenadrine and N,N-didemethyl orphenadrine.
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- Route of elimination
Not Available
- Half-life
13-20 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
Oral, mouse LD50 = 100 mg/kg; oral, rat LD50 = 255 mg/kg
- Pathways
Pathway Category Orphenadrine H1-Antihistamine Action 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 software1,2-Benzodiazepine 1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine. Abametapir The serum concentration of Orphenadrine can be increased when it is combined with Abametapir. Abemaciclib The metabolism of Abemaciclib can be decreased when combined with Orphenadrine. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Orphenadrine. Acebutolol The metabolism of Acebutolol can be decreased when combined with Orphenadrine. - Food Interactions
- Avoid alcohol.
- Take with or without food. Food does not significantly affect absorption.
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 Orphenadrine citrate X0A40N8I4S 4682-36-4 MMMNTDFSPSQXJP-UHFFFAOYSA-N Orphenadrine hydrochloride UBY910DUXH 341-69-5 UQZKYYIKWZOKKD-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Antiflex / Banflex / Biorphen / Disipal / Flexoject / Mio-Rel / OrfenAce / Orfro
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Disipal Tab 50mg Tablet 50 mg Oral 3 M Pharmaceuticals, A Division Of 3 M Canada Company 1957-12-31 2002-07-09 Canada 
Norflex Tablet, extended release 100 mg/1 Oral Physicians Total Care, Inc. 1995-04-06 2011-05-31 US 
Norflex Tablet, extended release 100000 ug/1 Oral 3M Company 1959-11-04 2006-12-29 US Norflex Injection 60 mg/2mL Intramuscular; Intravenous 3M Company 1960-10-02 2006-12-29 US Norflex Injection 60 mg/2mL Intramuscular; Intravenous Graceway Pharmaceuticals 2010-05-25 2010-12-31 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Orphenadrine Citrate Tablet, extended release 100 mg/1 Oral Lake Erie Medical Dba Quality Care Produts Llc 2000-02-15 2015-12-31 US Orphenadrine Citrate Tablet, extended release 100 mg/1 Oral A-S Medication Solutions 1998-06-19 Not applicable US 
Orphenadrine Citrate Tablet, extended release 100 mg/1 Oral Direct Rx 2019-08-29 Not applicable US Orphenadrine Citrate Tablet, extended release 100 mg/1 Oral Woodward Pharma Services Llc 2017-05-26 Not applicable US Orphenadrine Citrate Tablet, extended release 100 mg/1 Oral American Health Packaging 2014-09-09 2020-10-31 US - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Norflex Tablet, extended release 100 mg Oral Valeant Canada Lp Valeant Canada S.E.C. 1993-12-31 2014-07-30 Canada Orfenace Tablet 100mg Tablet 100 mg Oral Sterimax Inc 1994-12-31 Not applicable Canada Sandoz Orphenadrine Tablet, extended release 100 mg Oral Sandoz S.P.A. 2001-02-27 Not applicable Canada นอร์เฟลก Tablet, delayed release 100 mg บริษัท ไอโนวา ฟาร์มา (ประเทศไทย) จำกัด 2018-04-03 Not applicable Thailand 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image ANAREX TABLET Orphenadrine citrate (35 mg) + Acetaminophen (450 mg) Tablet Oral DUOPHARMA MANUFACTURING (BANGI) SDN. BHD. 2020-09-08 Not applicable Malaysia 
ANAREX TABLETS Orphenadrine citrate (35 mg) + Acetaminophen (450 mg) Tablet Oral BEACONS PHARMACEUTICALS PTE. LTD. 1991-03-30 Not applicable Singapore 
CAMGESIC TABLET Orphenadrine citrate (35 mg) + Acetaminophen (450 mg) Tablet Oral PHARMATECH RESOURCES (FE) PTE. LTD. 1998-02-07 Not applicable Singapore CETAGESIC TABLET Orphenadrine citrate (25 mg) + Acetaminophen (500 mg) Tablet Oral DUOPHARMA (SINGAPORE) PTE LTD 1991-04-22 Not applicable Singapore CORILAX PINK Orphenadrine citrate (35 mg) + Acetaminophen (450 mg) Tablet Oral บริษัท ชุมชนเภสัชกรรม จำกัด (มหาชน) 2004-03-17 Not applicable Thailand - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Norflex Orphenadrine citrate (100 mg/1) Tablet, extended release Oral Physicians Total Care, Inc. 1995-04-06 2011-05-31 US
Categories
- ATC Codes
- M03BC51 — Orphenadrine, combinations
- M03BC — Ethers, chemically close to antihistamines
- M03B — MUSCLE RELAXANTS, CENTRALLY ACTING AGENTS
- M03 — MUSCLE RELAXANTS
- M — MUSCULO-SKELETAL SYSTEM
- N04AB — Ethers chemically close to antihistamines
- N04A — ANTICHOLINERGIC AGENTS
- N04 — ANTI-PARKINSON DRUGS
- N — NERVOUS SYSTEM
- Drug Categories
- Agents producing tachycardia
- Amines
- Anti-Dyskinesia Agents
- Anti-Parkinson Drugs
- Anticholinergic Agents
- Autonomic Agents
- Benzene Derivatives
- Benzhydryl Compounds
- Central Nervous System Agents
- Central Nervous System Depressants
- Centrally-mediated Muscle Relaxation
- Cholinergic Agents
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strong)
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strong)
- Cytochrome P-450 CYP2E1 Inhibitors
- Cytochrome P-450 CYP2E1 Inhibitors (strength unknown)
- 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
- Enzyme Inhibitors
- Ethers, Chemically Close to Antihistamines
- Ethylamines
- Histamine Antagonists
- Histamine H1 Antagonists
- Miscellaneous Skeletal Muscle Relaxants
- Muscarinic Antagonists
- Muscle Relaxants
- Muscle Relaxants, Centrally Acting Agents
- Musculo-Skeletal System
- Nervous System
- Neurotransmitter Agents
- NMDA Receptor Antagonists
- Parasympatholytics
- Peripheral Nervous System Agents
- Potential QTc-Prolonging Agents
- QTc Prolonging 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
- Benzylethers / Toluenes / Trialkylamines / Dialkyl ethers / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Amine / Aromatic homomonocyclic compound / Benzylether / Dialkyl ether / Diphenylmethane / Ether / Hydrocarbon derivative / Organic nitrogen compound / Organic oxygen compound / Organonitrogen compound
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- tertiary amino compound, ether (CHEBI:7789)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- AL805O9OG9
- CAS number
- 83-98-7
- InChI Key
- QVYRGXJJSLMXQH-UHFFFAOYSA-N
- InChI
- InChI=1S/C18H23NO/c1-15-9-7-8-12-17(15)18(20-14-13-19(2)3)16-10-5-4-6-11-16/h4-12,18H,13-14H2,1-3H3
- IUPAC Name
- dimethyl({2-[(2-methylphenyl)(phenyl)methoxy]ethyl})amine
- SMILES
- CN(C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1C
References
- General References
- Ji D, Sui ZY, Ma YY, Luo F, Cui CL, Han JS: NMDA receptor in nucleus accumbens is implicated in morphine withdrawal in rats. Neurochem Res. 2004 Nov;29(11):2113-20. [Article]
- External Links
- Human Metabolome Database
- HMDB0015304
- KEGG Drug
- D08305
- KEGG Compound
- C07935
- PubChem Compound
- 4601
- PubChem Substance
- 46506085
- ChemSpider
- 4440
- BindingDB
- 50062614
- 7715
- ChEBI
- 7789
- ChEMBL
- CHEMBL900
- Therapeutic Targets Database
- DAP000858
- PharmGKB
- PA450715
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Orphenadrine
- FDA label
- Download (247 KB)
- MSDS
- Download (73.6 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 Musculoskeletal Disorders / Pain Management 1 somestatus stop reason just information to hide Not Available Completed Treatment Analgesia 1 somestatus stop reason just information to hide Not Available Terminated Treatment Cirrhosis of the Liver 1 somestatus stop reason just information to hide Not Available Withdrawn Treatment Pain Relief 1 somestatus stop reason just information to hide 4 Completed Supportive Care Pain Management / Posterior Spinal Fusion 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Abraxis BioScience Inc.
- Actavis Group
- Aidarex Pharmacuticals LLC
- Alba Pharmacal
- A-S Medication Solutions LLC
- Avkare Incorporated
- Bedford Labs
- Ben Venue Laboratories Inc.
- Bryant Ranch Prepack
- Clint Pharmaceutical Inc.
- Corepharma LLC
- DispenseXpress Inc.
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Eon Labs
- Gallipot
- Gavis Pharmaceuticals LLC
- Global Pharmaceuticals
- Graceway Pharmaceuticals
- H.J. Harkins Co. Inc.
- Impax Laboratories Inc.
- Innoviant Pharmacy Inc.
- International Ethical Labs Inc.
- Kiel Laboratories Inc.
- Lake Erie Medical and Surgical Supply
- Major Pharmaceuticals
- Murfreesboro Pharmaceutical Nursing Supply
- Nucare Pharmaceuticals Inc.
- Palmetto Pharmaceuticals Inc.
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pharma Pac LLC
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmedix
- Physicians Total Care Inc.
- Preferred Pharmaceuticals Inc.
- Prepak Systems Inc.
- Rebel Distributors Corp.
- Redpharm Drug
- Resource Optimization and Innovation LLC
- Sandhills Packaging Inc.
- Sandoz
- Southwood Pharmaceuticals
- St Mary's Medical Park Pharmacy
- Stat Rx Usa
- Watson Pharmaceuticals
- Dosage Forms
Form Route Strength Tablet Oral 35 mg Tablet Oral 25 mg Tablet, coated Oral 50 MG Solution Parenteral 60.00 mg Solution Parenteral Injection Intramuscular; Intravenous 60 mg/2mL Liquid Intramuscular; Intravenous 30 mg / mL Tablet, extended release Oral 100 mg/1 Tablet, extended release Oral 100000 ug/1 Tablet Oral Capsule Oral Tablet, film coated Oral 250 mg Injection Intramuscular; Intravenous 30 mg/1mL Injection, solution Intramuscular; Intravenous 30 mg/1mL Tablet Oral 100 mg/1 Tablet Oral Tablet, multilayer Oral Solution Parenteral 60.000 mg Tablet, extended release Oral 100 mg Tablet, delayed release 100 mg Tablet, film coated Tablet Oral 70 mg Tablet, film coated 100 mg Tablet, coated Oral Tablet Oral 100 mg Tablet Oral 50 mg - Prices
Unit description Cost Unit Norflex 30 mg/ml ampul 14.31USD ml Orphenadrine 30 mg/ml ampule 11.25USD ml Orphenadrine Compound-DS 50-770-60 mg tablet 2.94USD tablet Orphenadrine comp forte tablet 2.84USD tablet Norflex er 100 mg tablet 2.67USD tablet Norflex 100 mg tablet sa 2.64USD tablet Orphenadrine Citrate CR 100 mg 12 Hour tablet 2.26USD tablet Orphenadrine er 100 mg tablet 2.17USD tablet Orphenadrine citrate powder 1.6USD g Orphenadrine comp tablet 1.31USD tablet 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) < 25 °C PhysProp boiling point (°C) 195 °C at 1.20E+01 mm Hg PhysProp water solubility Sparingly soluble in water Not Available logP 3.77 SANGSTER (1993) pKa 8.91 SANGSTER (1994) - Predicted Properties
Property Value Source Water Solubility 0.03 mg/mL ALOGPS logP 3.5 ALOGPS logP 4.17 Chemaxon logS -4 ALOGPS pKa (Strongest Basic) 8.87 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 12.47 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 84.97 m3·mol-1 Chemaxon Polarizability 31.83 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9881 Blood Brain Barrier + 0.9134 Caco-2 permeable + 0.8654 P-glycoprotein substrate Substrate 0.6196 P-glycoprotein inhibitor I Inhibitor 0.5825 P-glycoprotein inhibitor II Non-inhibitor 0.6378 Renal organic cation transporter Inhibitor 0.7359 CYP450 2C9 substrate Non-substrate 0.7658 CYP450 2D6 substrate Substrate 0.8918 CYP450 3A4 substrate Substrate 0.6958 CYP450 1A2 substrate Non-inhibitor 0.6363 CYP450 2C9 inhibitor Non-inhibitor 0.9191 CYP450 2D6 inhibitor Inhibitor 0.8949 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.9363 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5979 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.6341 Biodegradation Not ready biodegradable 0.9422 Rat acute toxicity 2.8405 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.5224 hERG inhibition (predictor II) Inhibitor 0.7052
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 169.6026427 predictedDarkChem Lite v0.1.0 [M-H]- 160.14406 predictedDeepCCS 1.0 (2019) [M+H]+ 169.6315427 predictedDarkChem Lite v0.1.0 [M+H]+ 162.50206 predictedDeepCCS 1.0 (2019) [M+Na]+ 169.8909427 predictedDarkChem Lite v0.1.0 [M+Na]+ 168.5952 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
- Antagonist
- General Function
- Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:27616483, PubMed:28126851, PubMed:9489750). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:9489750)
- Specific Function
- glutamate binding
- Gene Name
- GRIN2D
- Uniprot ID
- O15399
- Uniprot Name
- Glutamate receptor ionotropic, NMDA 2D
- Molecular Weight
- 143750.685 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]
- Kornhuber J, Parsons CG, Hartmann S, Retz W, Kamolz S, Thome J, Riederer P: Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies. J Neural Transm Gen Sect. 1995;102(3):237-46. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:26875626, PubMed:26919761, PubMed:28105280, PubMed:28126851, PubMed:7685113). Sensitivity to glutamate and channel kinetics depend on the subunit composition (PubMed:26919761)
- Specific Function
- amyloid-beta binding
- Gene Name
- GRIN1
- Uniprot ID
- Q05586
- Uniprot Name
- Glutamate receptor ionotropic, NMDA 1
- Molecular Weight
- 105371.945 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]
- Kornhuber J, Parsons CG, Hartmann S, Retz W, Kamolz S, Thome J, Riederer P: Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies. J Neural Transm Gen Sect. 1995;102(3):237-46. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine
- Specific Function
- calcium channel activity
- Gene Name
- GRIN3B
- Uniprot ID
- O60391
- Uniprot Name
- Glutamate receptor ionotropic, NMDA 3B
- Molecular Weight
- 112990.98 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]
- Kornhuber J, Parsons CG, Hartmann S, Retz W, Kamolz S, Thome J, Riederer P: Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies. J Neural Transm Gen Sect. 1995;102(3):237-46. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. During the development of neural circuits, plays a role in the synaptic refinement period, restricting spine maturation and growth. By competing with GIT1 interaction with ARHGEF7/beta-PIX, may reduce GIT1/ARHGEF7-regulated local activation of RAC1, hence affecting signaling and limiting the maturation and growth of inactive synapses. May also play a role in PPP2CB-NMDAR mediated signaling mechanism
- Specific Function
- calcium channel activity
- Gene Name
- GRIN3A
- Uniprot ID
- Q8TCU5
- Uniprot Name
- Glutamate receptor ionotropic, NMDA 3A
- Molecular Weight
- 125464.07 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]
- Kornhuber J, Parsons CG, Hartmann S, Retz W, Kamolz S, Thome J, Riederer P: Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies. J Neural Transm Gen Sect. 1995;102(3):237-46. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein-coupled receptor for histamine, a biogenic amine that functions as an immune modulator and a neurotransmitter (PubMed:33828102, PubMed:8280179). Through the H1 receptor, histamine mediates the contraction of smooth muscles and increases capillary permeability due to contraction of terminal venules. Also mediates neurotransmission in the central nervous system and thereby regulates circadian rhythms, emotional and locomotor activities as well as cognitive functions (By similarity)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HRH1
- Uniprot ID
- P35367
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 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]
- Rumore MM, Schlichting DA: Analgesic effects of antihistaminics. Life Sci. 1985 Feb 4;36(5):403-16. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (PubMed:2008212, PubMed:8125921). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921)
- Specific Function
- actin binding
- Gene Name
- SLC6A2
- Uniprot ID
- P23975
- Uniprot Name
- Sodium-dependent noradrenaline transporter
- Molecular Weight
- 69331.42 Da
References
- Pubill D, Canudas AM, Pallas M, Sureda FX, Escubedo E, Camins A, Camarasa J: Assessment of the adrenergic effects of orphenadrine in rat vas deferens. J Pharm Pharmacol. 1999 Mar;51(3):307-12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms
- Specific Function
- transmembrane transporter binding
- Gene Name
- SCN10A
- Uniprot ID
- Q9Y5Y9
- Uniprot Name
- Sodium channel protein type 10 subunit alpha
- Molecular Weight
- 220623.605 Da
References
- Pubill D, Canudas AM, Pallas M, Sureda FX, Escubedo E, Camins A, Camarasa J: Assessment of the adrenergic effects of orphenadrine in rat vas deferens. J Pharm Pharmacol. 1999 Mar;51(3):307-12. [Article]
Enzymes
- 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
- Peng FC, Lin Wu SW: Metabolism of territrem a in liver microsomes from male wistar rats: 3. Cytochrome p-450 isoforms catalyzing tra metabolism. J Toxicol Environ Health A. 2002 Dec 27;65(24):2163-75. [Article]
- Lin Wu SW, Jean WC, Peng FC, Edwards RJ: Cytochrome P-4503A1 catalyzes the formation of MA1 from territrem a in liver microsomes of 7-week-old female Wistar rats. J Toxicol Environ Health A. 2003 Mar 14;66(5):453-67. [Article]
- Chang TK, Weber GF, Crespi CL, Waxman DJ: Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer Res. 1993 Dec 1;53(23):5629-37. [Article]
- Stresser DM, Dehal SS, Kupfer D: Ring hydroxylation of [o-3H]methoxychlor as a probe for liver microsomal CYP2B activity: potential for in vivo CYP2B assay. Anal Biochem. 1996 Jan 1;233(1):100-7. [Article]
- Murray M, Fiala-Beer E, Sutton D: Upregulation of cytochromes P450 2B in rat liver by orphenadrine. Br J Pharmacol. 2003 Jun;139(4):787-96. [Article]
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [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
- Roos PH, Mahnke A: Metabolite complex formation of orphenadrine with cytochrome P450. Involvement of CYP2C11 and CYP3A isozymes. Biochem Pharmacol. 1996 Jul 12;52(1):73-84. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids (PubMed:10553002, PubMed:18577768). 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:10553002, PubMed:18577768). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids (PubMed:10553002, PubMed:18577768). May be involved in the oxidative metabolism of xenobiotics (Probable)
- Specific Function
- 4-nitrophenol 2-monooxygenase activity
- Gene Name
- CYP2E1
- Uniprot ID
- P05181
- Uniprot Name
- Cytochrome P450 2E1
- Molecular Weight
- 56848.42 Da
References
- Sai Y, Dai R, Yang TJ, Krausz KW, Gonzalez FJ, Gelboin HV, Shou M: Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450. Xenobiotica. 2000 Apr;30(4):327-43. [Article]
- Sutrisna E: The Impact of CYP1A2 and CYP2E1 Genes Polymorphism on Theophylline Response. J Clin Diagn Res. 2016 Nov;10(11):FE01-FE03. doi: 10.7860/JCDR/2016/21067.8914. Epub 2016 Nov 1. [Article]
- Ekins S, VandenBranden M, Ring BJ, Wrighton SA: Examination of purported probes of human CYP2B6. Pharmacogenetics. 1997 Jun;7(3):165-79. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Data supported only by in vitro evidence.
- 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
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- 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
- Guo Z, Raeissi S, White RB, Stevens JC: Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos. 1997 Mar;25(3):390-3. [Article]
- Murray M, Fiala-Beer E, Sutton D: Upregulation of cytochromes P450 2B in rat liver by orphenadrine. Br J Pharmacol. 2003 Jun;139(4):787-96. [Article]
- Svensson US, Ashton M: Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol. 1999 Oct;48(4):528-35. doi: 10.1046/j.1365-2125.1999.00044.x. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- BinderRegulator
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Martinez-Gomez MA, Carril-Aviles MM, Sagrado S, Villanueva-Camanas RM, Medina-Hernandez MJ: Characterization of antihistamine-human serum protein interactions by capillary electrophoresis. J Chromatogr A. 2007 Apr 20;1147(2):261-9. doi: 10.1016/j.chroma.2007.02.054. Epub 2007 Feb 22. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 21, 2024 12:54