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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2016-02-11 01:32:19 UTC
HMDB IDHMDB15304
Secondary Accession NumbersNone
Metabolite Identification
Common NameOrphenadrine
DescriptionOrphenadrine is only found in individuals that have used or taken this drug. It is a muscarinic antagonist used to treat drug-induced parkinsonism and to relieve pain from muscle spasm. [PubChem]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.
Structure
Thumb
Synonyms
ValueSource
2-(Phenyl-O-tolylmethoxy)ethyldimethylamineChEBI
2-MethyldiphenhydramineChEBI
beta-Dimethylaminoethyl 2-methylbenzhydryl etherChEBI
Dimethyl-[2-(phenyl-O-tolyl-methoxy)-ethyl]-amineChEBI
N,N-Dimethyl-2-(alpha-2-tolylbenzoyloxy)ethylamineChEBI
N,N-Dimethyl-2-(phenyl(O-tolyl)methoxy)ethanamineChEBI
N,N-Dimethyl-2-[(O-methyl-alpha-phenylbenzyl)oxy]ethylamineChEBI
O-MethyldiphenhydramineChEBI
O-MonomethyldiphenhydramineChEBI
OrfenadrinaChEBI
OrphenadrinumChEBI
Phenyl-O-tolylmethyl dimethyaminoethyl etherChEBI
b-Dimethylaminoethyl 2-methylbenzhydryl etherGenerator
β-dimethylaminoethyl 2-methylbenzhydryl etherGenerator
MephenamineHMDB
OrphenadineHMDB
OrphenadrinHMDB
Orphenadrine citrateHMDB
OrphenateHMDB
OrphenedrineHMDB
Chemical FormulaC18H23NO
Average Molecular Weight269.3813
Monoisotopic Molecular Weight269.177964363
IUPAC Namedimethyl({2-[(2-methylphenyl)(phenyl)methoxy]ethyl})amine
Traditional Nameorphenadrine
CAS Registry Number83-98-7
SMILES
CN(C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1C
InChI Identifier
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
InChI KeyInChIKey=QVYRGXJJSLMXQH-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Benzylether
  • Toluene
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antidyskinetics
  • Antiparkinson Agents
  • Muscarinic Antagonists
  • Muscle Relaxants, Central
  • Parasympatholytics
  • Skeletal Muscle Relaxants
Application
  • Pharmaceutical
Cellular locations
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point156 - 157 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility3.00e-02 g/LNot Available
LogP3.6Not Available
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 RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-0a4i-9200000000-213fd17f1f5014e79c8bView in MoNA
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01173
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01173
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-4 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-2 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01173
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4440
KEGG Compound IDC07935
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkOrphenadrine
NuGOwiki LinkHMDB15304
Metagene LinkHMDB15304
METLIN IDNot Available
PubChem Compound4601
PDB IDNot Available
ChEBI ID7789
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
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. [15662845 ]

Enzymes

General function:
Involved in monooxygenase 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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. [8678911 ]
General function:
Involved in monooxygenase 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 or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular weight:
56848.42
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. [10821163 ]
General function:
Involved in monooxygenase 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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular weight:
56277.81
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. [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. [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. [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. [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. [12813002 ]
General function:
Involved in ionotropic 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. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors
Gene Name:
GRIN1
Uniprot ID:
Q05586
Molecular weight:
105371.9
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. [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. [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. [8788072 ]
General function:
Involved in ionotropic 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
Molecular weight:
112991.0
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. [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. [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. [8788072 ]
General function:
Involved in ionotropic 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
Molecular weight:
143750.7
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. [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. [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. [8788072 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular weight:
55783.6
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. [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. [17016423 ]
  3. Rumore MM, Schlichting DA: Analgesic effects of antihistaminics. Life Sci. 1985 Feb 4;36(5):403-16. [2578597 ]
General function:
Involved in ionotropic 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. May play a role in the development of dendritic spines. May play a role in PPP2CB-NMDAR mediated signaling mechanism
Gene Name:
GRIN3A
Uniprot ID:
Q8TCU5
Molecular weight:
125464.1
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. [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. [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. [8788072 ]
General function:
Involved in ion channel activity
Specific function:
This protein 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. It is a tetrodotoxin-resistant sodium channel isoform. Its electrophysiological properties vary depending on the type of the associated beta subunits (in vitro). Plays a role in neuropathic pain mechanisms
Gene Name:
SCN10A
Uniprot ID:
Q9Y5Y9
Molecular weight:
220623.6
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. [10344632 ]

Transporters

General function:
Involved in neurotransmitter: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
Molecular weight:
69331.42
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. [10344632 ]