Details
Stereochemistry | RACEMIC |
Molecular Formula | C18H23NO.C6H8O7 |
Molecular Weight | 461.5048 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)CC(O)(CC(O)=O)C(O)=O.CN(C)CCOC(C1=CC=CC=C1)C2=C(C)C=CC=C2
InChI
InChIKey=MMMNTDFSPSQXJP-UHFFFAOYSA-N
InChI=1S/C18H23NO.C6H8O7/c1-15-9-7-8-12-17(15)18(20-14-13-19(2)3)16-10-5-4-6-11-16;7-3(8)1-6(13,5(11)12)2-4(9)10/h4-12,18H,13-14H2,1-3H3;13H,1-2H2,(H,7,8)(H,9,10)(H,11,12)
DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Prntlbl.pdfCurator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Prntlbl.pdf
Curator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html
Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs. 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. 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 anesthetic 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 favorable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. Adverse reactions of orphenadrine citrate are mainly due to the mild anticholinergic action of orphenadrine citrate and are usually associated with higher dosage. Dryness of the mouth is usually the first adverse effect to appear. When the daily dose is increased, possible adverse effects include tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilatation of pupils, increased ocular tension, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness, hypersensitivity reactions, pruritus, hallucinations, agitation, tremor, gastric irritation and rarely urticaria and other dermatoses
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22793499 |
97.7 µM [IC50] | ||
Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9464369 |
6.0 µM [Ki] | ||
Target ID: CHEMBL2094109 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3353357 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | DISIPAL Approved UseOrphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Launch Date1957 |
|||
Primary | DISIPAL Approved UseOrphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Launch Date1957 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
41.89 ng/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
49.19 ng/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1739.15 ng × h/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
1772.44 ng × h/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
21.02 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
22.29 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7% |
ORPHENADRINE plasma | Homo sapiens |
Doses
Dose | Population | Adverse events |
---|---|---|
500 mg 1 times / day steady, oral Highest studied dose Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: |
unhealthy, adult Health Status: unhealthy Condition: depression Age Group: adult Sources: |
|
2 g single, intramuscular Overdose Dose: 2 g Route: intramuscular Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: |
2 g single, intravenous Overdose Dose: 2 g Route: intravenous Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: |
2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Toxic reaction (NOS) | grade 5 | 2 g single, intramuscular Overdose Dose: 2 g Route: intramuscular Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Toxic reaction (NOS) | grade 5 | 2 g single, intravenous Overdose Dose: 2 g Route: intravenous Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Toxic reaction (NOS) | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
partial | ||||
partial | ||||
partial | ||||
partial | ||||
strong | ||||
strong | ||||
strong | ||||
weak [IC50 65 uM] | ||||
weak [IC50 >100 uM] | ||||
weak [IC50 >100 uM] | ||||
yes [IC50 2.5 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/12813002/ |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Prochlorperazine in childhood: side-effects. | 1977 |
|
Anticholinergics for symptomatic management of Parkinson's disease. | 2003 |
|
Therapeutic response of benzodiazepine, orphenadrine citrate and occlusal splint association in TMD pain. | 2003 Apr |
|
Upregulation of cytochromes P450 2B in rat liver by orphenadrine. | 2003 Jun |
|
Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats. | 2003 Nov |
|
[Diclofenac 75mg. and 30 mg. orfenadine (Neodolpasse) versus placebo and piroxicam in postoperative analgesia after arthroscopy]. | 2004 |
|
Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review. | 2004 Aug |
|
Drug-drug interactions of Z-338, a novel gastroprokinetic agent, with terfenadine, comparison with cisapride, and involvement of UGT1A9 and 1A8 in the human metabolism of Z-338. | 2004 Aug 23 |
|
Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. | 2004 Jan 12 |
|
Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer. | 2004 Jan 12 |
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Alternatives to levodopa in the initial treatment of early Parkinson's disease. | 2005 |
|
Primary chemotherapy with gemcitabine, epirubicin and taxol (GET) in operable breast cancer: a phase II study. | 2005 Aug 22 |
|
Dimemorfan N-demethylation by mouse liver microsomal cytochrome P450 enzymes. | 2005 Jul 1 |
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Benzodiazepine prescribing behaviour and attitudes: a survey among general practitioners practicing in northern Thailand. | 2005 Jun 23 |
|
Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous ipriflavone in rats. | 2006 Apr |
|
Catanionic mixtures involving a drug: a rather general concept that can be utilized for prolonged drug release from gels. | 2006 Apr |
|
Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune diabetes: focus on the choice of anti-H1 drugs. | 2006 Dec |
|
Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous omeprazole in rats. | 2006 Jul |
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Pharmacokinetic study of orphenadrine using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). | 2006 Jul 24 |
|
Restless legs syndrome: diagnosis and review of management options. | 2006 Jun |
|
A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer. | 2006 May 24 |
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Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a phase I-II study. | 2006 May 8 |
|
OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. | 2006 Nov |
|
Effects of enzyme inducers and inhibitors on the pharmacokinetics of metformin in rats: involvement of CYP2C11, 2D1 and 3A1/2 for the metabolism of metformin. | 2006 Oct |
|
Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery. | 2006 Sep |
|
Acute adverse cutaneous reaction after the concomitant use of venlafaxine and orphenadrine citrate plus paracetamol in a depressed patient. | 2006 Sep |
|
Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction. | 2006 Sep |
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Anticholinergic drug-induced delirium in an elderly Alzheimer's dementia patient. | 2007 |
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Characterization of antihistamine-human serum protein interactions by capillary electrophoresis. | 2007 Apr 20 |
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Enantiomeric quality control of antihistamines in pharmaceuticals by affinity electrokinetic chromatography with human serum albumin as chiral selector. | 2007 Jun 5 |
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Parkinson's disease and dopaminergic therapy--differential effects on movement, reward and cognition. | 2008 Aug |
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Effect of warnings in a medical journal on the use of orphenadrine. | 2008 Aug |
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Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration. | 2008 Dec |
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Are there alternatives to the use of quinine to treat nocturnal leg cramps? | 2008 Feb |
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Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells. | 2008 May |
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Demographics of toxic exposures presenting to three public hospital emergency departments in Singapore 2001-2003. | 2009 Apr |
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Involvement of voltage-gated sodium channels blockade in the analgesic effects of orphenadrine. | 2009 Apr |
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The use of antipsychotic and anticholinergic antiparkinson drugs in Norway after the withdrawal of orphenadrine. | 2009 Aug |
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Evaluation of luciferin-isopropyl acetal as a CYP3A4 substrate for human hepatocytes: effects of organic solvents, cytochrome P450 (P450) inhibitors, and P450 inducers. | 2009 Aug |
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The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study. | 2009 Feb |
|
Effects of cytochrome P450 inducers and inhibitors on the pharmacokinetics of intravenous furosemide in rats: involvement of CYP2C11, 2E1, 3A1 and 3A2 in furosemide metabolism. | 2009 Jan |
|
Fixed drug eruption resulting from fluconazole use: a case report. | 2009 Jul 6 |
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Drugs associated with more suicidal ideations are also associated with more suicide attempts. | 2009 Oct 2 |
|
Pharmacokinetics of mirodenafil, a new erectogenic, and its metabolite, SK3541, in rats: involvement of CYP1A1/2, 2B1/2, 2D subfamily, and 3A1/2 for the metabolism of both mirodenafil and SK3541. | 2010 |
|
Orphenadrinium picrate. | 2010 Dec 18 |
|
Orphenadrinium picrate picric acid. | 2010 Feb 24 |
|
(2-Methyl-phen-yl)(phen-yl)methanol. | 2010 Jul 31 |
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7-Benzyloxyresorufin-O-dealkylase activity as a marker for measuring cytochrome P450 CYP3A induction in mouse liver. | 2010 Mar 1 |
|
Opiate sparing effect of fixed combination of diclophenac and orphenadrine after unilateral total hip arthroplasty: A double-blind, randomized, placebo-controlled, multi-centre clinical trial. | 2010 Nov |
|
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011 Jul 14 |
Patents
Sample Use Guides
Acute musculoskeletal conditions: 100 mg orally twice a day (morning and evening) or 60 mg by intramuscular or intravenous injection. May repeat every 12 hours.
Quinine-resistant leg cramps: 100 mg orally at bedtime.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3353357
An aliquot (400 mkl) of the brain membrane suspension (0.14 mg of protein), 100 mkl of (-)3H-QNB (0.95 nM) (specific activity 46 Ci/mmol), and 50 mk1 of the competing drugs at various concentrations were preincubated for 10 min. and thereafter incubated for 60 min. at 25C in 50 mM Tris-HC1 buffer (PH 7.4). When binding to heart and lung membranes was studied, 500 nkl of homogenate (protein contents were 0.58 mg and 0.54 mg of rat heart and lung tissue and 0.63 mg of guinea pig lung tissue was added to tubes containing 500 mkl of 50 mM Tris-HC1 buffer (PH 7.4), 100 mk1 of (-)3H-QNB (final concentration 0.4 nM) and 100 mkl of buffer (total binding) or unlabeled Orphenadrine.
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Classification Tree | Code System | Code | ||
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WHO-ATC |
M03BC01
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NCI_THESAURUS |
C29696
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225-137-5
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DBSALT000400
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X0A40N8I4S
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7790
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100000092072
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7716
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CHEMBL900
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20846
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C47641
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4724-58-7
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NON-SPECIFIC STOICHIOMETRY | |||
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1479009
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4682-36-4
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m8245
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DTXSID8044678
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SUB03546MIG
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757238
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ACTIVE MOIETY
SUBSTANCE RECORD