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=CC=CC=C2C
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)
| Molecular Formula | C6H8O7 |
| Molecular Weight | 192.1235 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C18H23NO |
| Molecular Weight | 269.3813 |
| Charge | 0 |
| Count |
|
| Stereochemistry | RACEMIC |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Optical Activity | ( + / - ) |
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class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs.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 |
|
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 |
|---|---|---|
| Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011-07-14 |
|
| Orphenadrinium picrate. | 2010-12-18 |
|
| 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. | 2010-11 |
|
| Full recovery from a potentially lethal dose of orphenadrine ingestion using conservative treatment: a case report. | 2010-11 |
|
| (2-Methyl-phen-yl)(phen-yl)methanol. | 2010-07-31 |
|
| Pharmacologic management of chronic pain. | 2010-06 |
|
| Comprehensive identification of active compounds in tablets by flow-injection data-dependent tandem mass spectrometry combined with library search. | 2010-04-15 |
|
| Testosterone hydroxylation in bovine liver: enzyme kinetic and inhibition study. | 2010-04 |
|
| 7-Benzyloxyresorufin-O-dealkylase activity as a marker for measuring cytochrome P450 CYP3A induction in mouse liver. | 2010-03-01 |
|
| Orphenadrinium picrate picric acid. | 2010-02-24 |
|
| 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 |
|
| Determination of orphenadrine plasma levels using HPLC with diode array detection and a novel solid-phase extraction procedure in psychiatric patients. | 2009-10-15 |
|
| Drugs associated with more suicidal ideations are also associated with more suicide attempts. | 2009-10-02 |
|
| The use of antipsychotic and anticholinergic antiparkinson drugs in Norway after the withdrawal of orphenadrine. | 2009-08 |
|
| Evaluation of luciferin-isopropyl acetal as a CYP3A4 substrate for human hepatocytes: effects of organic solvents, cytochrome P450 (P450) inhibitors, and P450 inducers. | 2009-08 |
|
| Fixed drug eruption resulting from fluconazole use: a case report. | 2009-07-06 |
|
| The first asymmetric halogen/metal-exchange reaction: desymmetrization of alcohols with enantiotopic bromoarene substituents. | 2009-07-06 |
|
| Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders. | 2009-06-03 |
|
| Demographics of toxic exposures presenting to three public hospital emergency departments in Singapore 2001-2003. | 2009-04 |
|
| Concordant up-regulation of cytochrome P450 Cyp3a11, testosterone oxidation and androgen receptor expression in mouse brain after xenobiotic treatment. | 2009-04 |
|
| Involvement of voltage-gated sodium channels blockade in the analgesic effects of orphenadrine. | 2009-04 |
|
| Physiological and pathological role of alpha-synuclein in Parkinson's disease through iron mediated oxidative stress; the role of a putative iron-responsive element. | 2009-03 |
|
| The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study. | 2009-02 |
|
| Influence of orphenadrine upon the protective activity of various antiepileptics in the maximal electroshock-induced convulsions in mice. | 2009-01-20 |
|
| 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. | 2009-01 |
|
| Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition. | 2008-12 |
|
| Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration. | 2008-12 |
|
| [Diclofenac/orphenadrine as a combined analgetic in post-operative relief of pain]. | 2008-09-28 |
|
| Parkinson's disease and dopaminergic therapy--differential effects on movement, reward and cognition. | 2008-08 |
|
| Effect of warnings in a medical journal on the use of orphenadrine. | 2008-08 |
|
| Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells. | 2008-05 |
|
| Genetic and chemical modifiers of a CUG toxicity model in Drosophila. | 2008-02-13 |
|
| Are there alternatives to the use of quinine to treat nocturnal leg cramps? | 2008-02 |
|
| Effects of CYP inducers and inhibitors on the pharmacokinetics of intravenous theophylline in rats: involvement of CYP1A1/2 in the formation of 1,3-DMU. | 2008-01 |
|
| Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656. | 2007-12 |
|
| Determination of paracetamol and orphenadrine citrate in pharmaceutical tablets by modeling of spectrophotometric data using partial least-squares and artificial neural networks. | 2007-10 |
|
| Evaluation of enantioselective binding of basic drugs to plasma by ACE. | 2007-08 |
|
| Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE. | 2007-08 |
|
| [Enzyme kinetics of schizandrin metabolism and sex differences in rat liver microsomes]. | 2007-07 |
|
| Enantiomeric quality control of antihistamines in pharmaceuticals by affinity electrokinetic chromatography with human serum albumin as chiral selector. | 2007-06-05 |
|
| Characterization of antihistamine-human serum protein interactions by capillary electrophoresis. | 2007-04-20 |
|
| Anticholinergic drug-induced delirium in an elderly Alzheimer's dementia patient. | 2007 |
|
| Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune diabetes: focus on the choice of anti-H1 drugs. | 2006-12 |
|
| OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. | 2006-11 |
|
| 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. | 2006-10 |
|
| Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery. | 2006-09 |
|
| Restless legs syndrome: diagnosis and review of management options. | 2006-06 |
|
| [Comparative study between botulin toxin and bupivacaine for triggering-points infiltration in chronic myofascial syndrome.]. | 2005-04 |
|
| Reversal of orphenadrine-induced ventricular tachycardia with physostigmine. | 1991-11-01 |
|
| Prochlorperazine in childhood: side-effects. | 1977 |
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.
| Substance Class |
Chemical
Created
by
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on
Edited
Mon Mar 31 18:40:33 GMT 2025
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| Record UNII |
X0A40N8I4S
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| Record Status |
Validated (UNII)
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| Record Version |
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WHO-ATC |
M03BC01
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NCI_THESAURUS |
C29696
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| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
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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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X0A40N8I4S
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757238
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| Related Record | Type | Details | ||
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (TITRATION)
EP
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BASIS OF STRENGTH->SUBSTANCE |
ASSAY (HPLC)
USP
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PARENT -> SALT/SOLVATE |
| Related Record | Type | Details | ||
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IMPURITY -> PARENT |
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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ACTIVE MOIETY |