Banner
targets (7) enzymes (3)
for drugs
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Mephenamine
O-Methyldiphenhydramine
Orphenadine
Orphenadrin
Orphenadrine Citrate
Orphenate
Orphenedrine
Salts Not Available
Brand names
Name Company
Antiflex
Biorphen
Brocadisipal
Brocasipal
Disipal
Flexoject
Mio-Rel
Myolin
Myotrol
Norflex
Orfro
First Prev Next Last
Brand mixtures Not Available
Categories
  • Skeletal Muscle Relaxants
  • Antiparkinson Agents
  • Antidyskinetics
  • Muscarinic Antagonists
  • Muscle Relaxants, Central
  • Parasympatholytics
CAS number 83-98-7
Weight Average: 269.3813
Monoisotopic: 269.177964363
Chemical Formula C18H23NO
InChI Key InChIKey=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
Plain Text
IUPAC Name
dimethyl({2-[(2-methylphenyl)(phenyl)methoxy]ethyl})amine
SMILES
CN(C)CCOC(C1=CC=CC=C1)C1=CC=CC=C1C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Diphenhydramines
Substructures
  • Diphenhydramines
  • Benzyl Alcohols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Diphenylmethanes
  • Aromatic compounds
Pharmacology
Indication Indicated for the treatment of Parkinson's disease.
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.
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Orphenadrine
    		N-demethyl orphenadrine Details
    Orphenadrine
      		N,N-didemethyl orphenadrine Details
      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 Not Available
      Pharmacoeconomics
      Manufacturers
      • Graceway pharmaceuticals llc
      • Akorn inc
      • Bedford laboratories
      • Watson laboratories inc
      • Ascot hosp pharmaceuticals inc div travenol laboratories inc
      • Gavis pharmaceuticals llc
      • Impax pharmaceuticals
      • Kiel laboratories inc
      • Sandoz inc
      • 3m pharmaceuticals inc
      Packagers
      Dosage forms
      Form Route Strength
      Liquid Intravenous
      Tablet Oral
      Tablet, extended release Oral
      Prices
      Unit description Cost Unit
      Norflex 30 mg/ml ampul 14.31 USD ml
      Orphenadrine 30 mg/ml ampule 11.25 USD ml
      Orphenadrine Compound-DS 50-770-60 mg tablet 2.94 USD tablet
      Orphenadrine comp forte tablet 2.84 USD tablet
      Norflex er 100 mg tablet 2.67 USD tablet
      Norflex 100 mg tablet sa 2.64 USD tablet
      Orphenadrine Citrate CR 100 mg 12 Hour tablet 2.26 USD tablet
      Orphenadrine er 100 mg tablet 2.17 USD tablet
      Orphenadrine citrate powder 1.6 USD g
      Orphenadrine comp tablet 1.31 USD 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 < 25 °C PhysProp
      boiling point 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 3.00e-02 g/l 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 ChemAxon
      rotatable bond count 6 ChemAxon
      refractivity 84.97 ChemAxon
      polarizability 31.83 ChemAxon
      References
      Synthesis Reference Not Available
      General Reference
      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
      External Links
      Resource Link
      KEGG Compound C07935 Link_out
      PubChem Compound 4601 Link_out
      PubChem Substance 46506085 Link_out
      ChemSpider 4440 Link_out
      ChEBI 7789 Link_out
      ChEMBL 7789 Link_out
      Therapeutic Targets Database DAP000858 Link_out
      PharmGKB PA450715 Link_out
      Drug Product Database 2243559 Link_out
      RxList http://www.rxlist.com/cgi/generic/orphen.htm Link_out
      Drugs.com http://www.drugs.com/cdi/orphenadrine.html Link_out
      Wikipedia http://en.wikipedia.org/wiki/Orphenadrine Link_out
      ATC Codes
      • M03BC01
      • N04AB02
      AHFS Codes
      • 12:20.00
      PDB Entries Not Available
      FDA label show (247 KB)
      MSDS show (73.6 KB)
      Interactions
      Drug Interactions
      Drug Interaction
      Docetaxel Orphenadrine may increase the serum levels and toxicity of docetaxel.
      Donepezil Possible antagonism of action
      Galantamine Possible antagonism of action
      Haloperidol The anticholinergic increases the risk of psychosis and tardive dyskinesia
      Rivastigmine Possible antagonism of action
      Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Orphenadrine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
      Trimethobenzamide Trimethobenzamide and Orphenadrine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
      Triprolidine Triprolidine and Orphenadrine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
      Trospium Trospium and Orphenadrine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
      Food Interactions
      • Take without regard to meals. Avoid alcohol.
      Targets

      1. Glutamate [NMDA] receptor subunit epsilon-4

      Pharmacological action: yes
      Actions: antagonist

      NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine

      Organism class: human
      UniProt ID: O15399 Link_out
      Gene: GRIN2D Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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

      2. Glutamate [NMDA] receptor subunit zeta-1

      Pharmacological action: yes
      Actions: antagonist

      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

      Organism class: human
      UniProt ID: Q05586 Link_out
      Gene: GRIN1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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

      3. Glutamate [NMDA] receptor subunit 3B

      Pharmacological action: yes
      Actions: antagonist

      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

      Organism class: human
      UniProt ID: O60391 Link_out
      Gene: GRIN3B Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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

      4. Glutamate [NMDA] receptor subunit 3A

      Pharmacological action: yes
      Actions: antagonist

      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

      Organism class: human
      UniProt ID: Q8TCU5 Link_out
      Gene: GRIN3A Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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

      5. Histamine H1 receptor

      Pharmacological action: yes
      Actions: antagonist

      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

      Organism class: human
      UniProt ID: P35367 Link_out
      Gene: HRH1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      3. Rumore MM, Schlichting DA: Analgesic effects of antihistaminics. Life Sci. 1985 Feb 4;36(5):403-16. Pubmed

      6. Sodium-dependent noradrenaline transporter

      Pharmacological action: yes
      Actions: inhibitor

      Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

      Organism class: human
      UniProt ID: P23975 Link_out
      Gene: SLC6A2 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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

      7. Sodium channel protein type 10 subunit alpha

      Pharmacological action: unknown
      Actions: inhibitor

      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

      Organism class: human
      UniProt ID: Q9Y5Y9 Link_out
      Gene: SCN10A Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      Enzymes

      1. Cytochrome P450 2B6

      Actions: inhibitor, inducer

      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

      UniProt ID: P20813 Link_out
      Gene: CYP2B6 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      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
      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
      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
      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

      2. Cytochrome P450 3A4

      Actions: substrate

      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. The enzyme also hydroxylates etoposide

      UniProt ID: P08684 Link_out
      Gene: CYP3A4
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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

      3. Cytochrome P450 2E1

      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

      UniProt ID: P05181 Link_out
      Gene: CYP2E1 Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      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
      Comments
      Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19