Identification

Name
Orphenadrine
Accession Number
DB01173  (APRD00097)
Type
Small Molecule
Groups
Approved
Description

A muscarinic antagonist used to treat drug-induced parkinsonism and to relieve pain from muscle spasm. [PubChem]

Structure
Thumb
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-alpha-phenylbenzyl)oxy]ethylamine
  • o-methyldiphenhydramine
  • o-monomethyldiphenhydramine
  • Orfenadrina
  • ORPHENADRINE
  • Orphenadrinum
  • Phenyl-O-tolylmethyl dimethyaminoethyl ether
  • β-dimethylaminoethyl 2-methylbenzhydryl ether
Product Ingredients
IngredientUNIICASInChI Key
Orphenadrine citrateX0A40N8I4S4682-36-4MMMNTDFSPSQXJP-UHFFFAOYSA-N
Orphenadrine hydrochlorideUBY910DUXH341-69-5UQZKYYIKWZOKKD-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Disipal Tab 50mgTablet50 mgOral3 M Pharmaceuticals, A Division Of 3 M Canada Company1957-12-312002-07-09Canada
NorflexInjection60 mg/2mLIntramuscular; IntravenousGraceway Pharmaceuticals2010-05-252010-12-31Us
NorflexInjection60 mg/2mLIntramuscular; Intravenous3M Company1960-10-022006-12-29Us
NorflexTablet, extended release100000 ug/1Oral3M Company1959-11-042006-12-29Us
NorflexLiquid30 mgIntramuscular; IntravenousValeant Canada Lp Valeant Canada S.E.C.1961-12-312014-07-30Canada
Orphenadrine Citrate Injection, USPLiquid30 mgIntramuscular; IntravenousSterimax Inc1996-12-02Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Orphenadrine CitrateTablet, extended release100 mg/1OralEon Labs, Inc.2000-02-15Not applicableUs
Orphenadrine CitrateTablet, extended release100 mg/1OralRed Pharm Drug, Inc.1998-06-19Not applicableUs
Orphenadrine CitrateInjection30 mg/1mLIntramuscular; IntravenousAkorn2006-10-17Not applicableUs
Orphenadrine CitrateTablet, extended release100 mg/1OralPhysicians Total Care, Inc.2000-04-17Not applicableUs54868 410220180907 15195 txv3x6
Orphenadrine CitrateTablet, extended release100 mg/1OralDirectrx2014-01-01Not applicableUs
Orphenadrine CitrateTablet100 mg/1OralPreferreed Pharmaceuticals Inc.2000-02-15Not applicableUs
Orphenadrine CitrateInjection, solution30 mg/1mLIntramuscular; IntravenousSagent Pharmaceuticals2011-10-01Not applicableUs
Orphenadrine CitrateTablet, extended release100 mg/1Oralbryant ranch prepack2000-02-15Not applicableUs
Orphenadrine CitrateTablet, extended release100 mg/1OralDirectrx2018-03-26Not applicableUs
Orphenadrine CitrateTablet100 mg/1OralAv Kare, Inc.2000-06-242015-02-20Us
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NorflexTablet, extended release100 mgOralValeant Canada Lp Valeant Canada S.E.C.1993-12-312014-07-30Canada
Orfenace Tablet 100mgTablet100 mgOralSterimax Inc1994-12-31Not applicableCanada
Sandoz OrphenadrineTablet, extended release100 mgOralSandoz Canada Incorporated2001-02-27Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NorgesicOrphenadrine citrate (50 mg/1) + Acetylsalicylic acid (770 mg/1) + Caffeine (60 mg/1)Tablet, multilayerOralPhysicians Total Care, Inc.1964-03-042006-12-31Us
NorgesicOrphenadrine citrate (25 mg/1) + Acetylsalicylic acid (385 mg/1) + Caffeine (30 mg/1)Tablet, multilayerOral3 M Pharmaceuticals1964-03-042015-12-31Us
Norgesic ForteOrphenadrine citrate (50 mg/1) + Acetylsalicylic acid (770 mg/1) + Caffeine (60 mg/1)Tablet, multilayerOral3 M Pharmaceuticals1964-03-042015-12-31Us
Norgesic Forte TabOrphenadrine citrate (50 mg) + Acetylsalicylic acid (770 mg) + Caffeine (60 mg)TabletOral3 M Pharmaceuticals, A Division Of 3 M Canada Company1976-12-312006-07-24Canada
Norgesic TabOrphenadrine citrate (25 mg) + Acetylsalicylic acid (385 mg) + Caffeine (30 mg)TabletOral3 M Pharmaceuticals, A Division Of 3 M Canada Company1964-12-312006-07-24Canada
Orphenadrine Citrate, Aspirin and CaffeineOrphenadrine citrate (50 mg/1) + Acetylsalicylic acid (770 mg/1) + Caffeine (60 mg/1)Tablet, multilayerOralEon Labs, Inc.1996-12-312014-11-30Us
Orphenadrine Citrate, Aspirin and CaffeineOrphenadrine citrate (50 mg/1) + Acetylsalicylic acid (770 mg/1) + Caffeine (60 mg/1)Tablet, multilayerOralRebel Distributors1996-12-31Not applicableUs
Orphenadrine Citrate, Aspirin and CaffeineOrphenadrine citrate (25 mg/1) + Acetylsalicylic acid (385 mg/1) + Caffeine (30 mg/1)Tablet, multilayerOralEon Labs, Inc.1996-12-312013-11-30Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NorflexOrphenadrine citrate (100 mg/1)Tablet, extended releaseOralPhysicians Total Care, Inc.1995-04-062011-05-31Us
International/Other Brands
Antiflex / Banflex / Biorphen / Disipal / Flexoject / Mio-Rel / Myolin / OrfenAce / Orfro
Categories
UNII
AL805O9OG9
CAS number
83-98-7
Weight
Average: 269.3813
Monoisotopic: 269.177964363
Chemical Formula
C18H23NO
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

Pharmacology

Indication

Indicated for the treatment of Parkinson's disease.

Associated Conditions
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.

TargetActionsOrganism
AGlutamate receptor ionotropic, NMDA 2D
antagonist
Human
AGlutamate receptor ionotropic, NMDA 1
antagonist
Human
AGlutamate receptor ionotropic, NMDA 3B
antagonist
Human
AGlutamate receptor ionotropic, NMDA 3A
antagonist
Human
AHistamine H1 receptor
antagonist
Human
ASodium-dependent noradrenaline transporter
inhibitor
Human
USodium channel protein type 10 subunit alpha
inhibitor
Human
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.

Route of elimination
Not Available
Half life

13-20 hours

Clearance
Not Available
Toxicity

Oral, mouse LD50 = 100 mg/kg; oral, rat LD50 = 255 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Orphenadrine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe risk or severity of adverse effects can be increased when Orphenadrine is combined with (2-benzhydryloxyethyl)diethyl-methylammonium iodide.
1,10-PhenanthrolineThe therapeutic efficacy of Orphenadrine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Orphenadrine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
5-methoxy-N,N-dimethyltryptamine5-methoxy-N,N-dimethyltryptamine may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
7-Nitroindazole7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
Food Interactions
  • Take without regard to meals. Avoid alcohol.

References

General References
  1. 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. [PubMed:15662845]
External Links
Human Metabolome Database
HMDB0015304
KEGG Compound
C07935
PubChem Compound
4601
PubChem Substance
46506085
ChemSpider
4440
BindingDB
50062614
ChEBI
7789
ChEMBL
CHEMBL900
Therapeutic Targets Database
DAP000858
PharmGKB
PA450715
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Orphenadrine
ATC Codes
M03BC51 — Orphenadrine, combinationsN04AB02 — Orphenadrine (chloride)M03BC01 — Orphenadrine (citrate)
AHFS Codes
  • 12:20.92 — Miscellaneous Skeletal Muscle Relaxants
FDA label
Download (247 KB)
MSDS
Download (73.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentOsteoarthritis of the Hands1
3Not Yet RecruitingTreatmentMechanical Low Back Pain / Postural Low Back Pain1
3RecruitingTreatmentLiver Cirrhosis / Muscle Cramps1
4CompletedTreatmentLow Back Pain (LBP)1
4CompletedTreatmentUnilateral Knee Arthroplasty1
4RecruitingSupportive CareColon Diverticulosis / Colonic Neoplasms / Constipation Drug Induced / Diverticulitis, Colonic / Ileus / Ileus paralytic / Ileus; Mechanical / Malignant Neoplasm of Colon / Occasional Constipation / Postoperative pain / Rectum Cancer / Rectum Neoplasm1
Not AvailableUnknown StatusTreatmentPain Relief1

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
FormRouteStrength
TabletOral50 mg
InjectionIntramuscular; Intravenous60 mg/2mL
LiquidIntramuscular; Intravenous30 mg
Tablet, extended releaseOral100 mg/1
Tablet, extended releaseOral100000 ug/1
TabletOral
TabletOral100 mg
InjectionIntramuscular; Intravenous30 mg/1mL
Injection, solutionIntramuscular; Intravenous30 mg/1mL
TabletOral100 mg/1
Tablet, multilayerOral
Tablet, extended releaseOral100 mg
Prices
Unit descriptionCostUnit
Norflex 30 mg/ml ampul14.31USD ml
Orphenadrine 30 mg/ml ampule11.25USD ml
Orphenadrine Compound-DS 50-770-60 mg tablet2.94USD tablet
Orphenadrine comp forte tablet2.84USD tablet
Norflex er 100 mg tablet2.67USD tablet
Norflex 100 mg tablet sa2.64USD tablet
Orphenadrine Citrate CR 100 mg 12 Hour tablet2.26USD tablet
Orphenadrine er 100 mg tablet2.17USD tablet
Orphenadrine citrate powder1.6USD g
Orphenadrine comp tablet1.31USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)< 25 °CPhysProp
boiling point (°C)195 °C at 1.20E+01 mm HgPhysProp
water solubilitySparingly soluble in waterNot Available
logP3.77SANGSTER (1993)
pKa8.91SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.03 mg/mLALOGPS
logP3.5ALOGPS
logP4.17ChemAxon
logS-4ALOGPS
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity84.97 m3·mol-1ChemAxon
Polarizability31.83 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9881
Blood Brain Barrier+0.9134
Caco-2 permeable+0.8654
P-glycoprotein substrateSubstrate0.6196
P-glycoprotein inhibitor IInhibitor0.5825
P-glycoprotein inhibitor IINon-inhibitor0.6378
Renal organic cation transporterInhibitor0.7359
CYP450 2C9 substrateNon-substrate0.7658
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.6958
CYP450 1A2 substrateNon-inhibitor0.6363
CYP450 2C9 inhibitorNon-inhibitor0.9191
CYP450 2D6 inhibitorInhibitor0.8949
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9363
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5979
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.6341
BiodegradationNot ready biodegradable0.9422
Rat acute toxicity2.8405 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5224
hERG inhibition (predictor II)Inhibitor0.7052
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-9200000000-213fd17f1f5014e79c8b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-e233c4258b887b1c4d95
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-6eb16a45ba9f222e4a96
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-46ad662bd87fac31bf96
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-1e90246098db8159dcdd
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-98528e097df59735a4a2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-b09cb35d4c4d1563eab0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-98fb2ac7e2a7b5389c76
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-f5b29d73b614d9a50c8c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-02t9-2900000000-5e46822ba471971d2ed4
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00lr-0900000000-02f47ad2686722a25761
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00lr-0900000000-c646cee3a03cb818670b

Taxonomy

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
Diphenylmethane / Benzylether / Toluene / Tertiary aliphatic amine / Tertiary amine / Ether / Dialkyl ether / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary amino compound, ether (CHEBI:7789)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Nmda glutamate receptor activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine.
Gene Name
GRIN2D
Uniprot ID
O15399
Uniprot Name
Glutamate receptor ionotropic, NMDA 2D
Molecular Weight
143750.685 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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. [PubMed:17016423]
  3. 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. [PubMed:8788072]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Voltage-gated cation channel activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic p...
Gene Name
GRIN1
Uniprot ID
Q05586
Uniprot Name
Glutamate receptor ionotropic, NMDA 1
Molecular Weight
105371.945 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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. [PubMed:17016423]
  3. 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. [PubMed:8788072]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Nmda glutamate receptor activity
Specific 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.
Gene Name
GRIN3B
Uniprot ID
O60391
Uniprot Name
Glutamate receptor ionotropic, NMDA 3B
Molecular Weight
112990.98 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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. [PubMed:17016423]
  3. 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. [PubMed:8788072]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein phosphatase 2a binding
Specific 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. May ...
Gene Name
GRIN3A
Uniprot ID
Q8TCU5
Uniprot Name
Glutamate receptor ionotropic, NMDA 3A
Molecular Weight
125464.07 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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. [PubMed:17016423]
  3. 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. [PubMed:8788072]
Details
5. Histamine H1 receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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. [PubMed:17016423]
  3. Rumore MM, Schlichting DA: Analgesic effects of antihistaminics. Life Sci. 1985 Feb 4;36(5):403-16. [PubMed:2578597]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. 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. [PubMed:10344632]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity
Specific 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 acro...
Gene Name
SCN10A
Uniprot ID
Q9Y5Y9
Uniprot Name
Sodium channel protein type 10 subunit alpha
Molecular Weight
220623.605 Da
References
  1. 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. [PubMed:10344632]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. 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. [PubMed:12515593]
  2. 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. [PubMed:12712632]
  3. 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. [PubMed:8242617]
  4. 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. [PubMed:8789153]
  5. 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. [PubMed:12813002]
  6. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]
  7. 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. [PubMed:9172960]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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. [PubMed:8678911]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. 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. [PubMed:10821163]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data supported only by in vitro evidence.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. 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. [PubMed:9172960]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:35