U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C18H23NO
Molecular Weight 269.3813
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ORPHENADRINE

SMILES

CN(C)CCOC(C1=CC=CC=C1)C2=C(C)C=CC=C2

InChI

InChIKey=QVYRGXJJSLMXQH-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description
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class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs.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

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
97.7 µM [IC50]
6.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DISIPAL

Approved Use

Orphenadrine 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 Date

-3.99081603E11
Primary
DISIPAL

Approved Use

Orphenadrine 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 Date

-3.99081603E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
7%
ORPHENADRINE plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse 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
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
2 g single, intravenous
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
2 g single, oral
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
AEs
PubMed

PubMed

TitleDatePubMed
Prochlorperazine in childhood: side-effects.
1977
Reversal of orphenadrine-induced ventricular tachycardia with physostigmine.
1991 Nov-Dec
[Comparative study between botulin toxin and bupivacaine for triggering-points infiltration in chronic myofascial syndrome.].
2005 Apr
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A.
2005 Feb 27
Benzodiazepine prescribing behaviour and attitudes: a survey among general practitioners practicing in northern Thailand.
2005 Jun 23
Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid-phase extraction and gas chromatography/mass spectrometry.
2006
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
Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous omeprazole in rats.
2006 Jul
Pharmacokinetic study of orphenadrine using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
2006 Jul 24
Torsades de pointes in congenital long QT syndrome following low-dose orphenadrine.
2006 May
A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer.
2006 May 24
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
Characterization of antihistamine-human serum protein interactions by capillary electrophoresis.
2007 Apr 20
Evaluation of enantioselective binding of basic drugs to plasma by ACE.
2007 Aug
Anticholinergic antiparkinson drug orphenadrine inhibits HERG channels: block attenuation by mutations of the pore residues Y652 or F656.
2007 Dec
[Enzyme kinetics of schizandrin metabolism and sex differences in rat liver microsomes].
2007 Jul
Enantiomeric quality control of antihistamines in pharmaceuticals by affinity electrokinetic chromatography with human serum albumin as chiral selector.
2007 Jun 5
Determination of paracetamol and orphenadrine citrate in pharmaceutical tablets by modeling of spectrophotometric data using partial least-squares and artificial neural networks.
2007 Oct
Parkinson's disease and dopaminergic therapy--differential effects on movement, reward and cognition.
2008 Aug
Are there alternatives to the use of quinine to treat nocturnal leg cramps?
2008 Feb
Genetic and chemical modifiers of a CUG toxicity model in Drosophila.
2008 Feb 13
Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells.
2008 May
Demographics of toxic exposures presenting to three public hospital emergency departments in Singapore 2001-2003.
2009 Apr
Concordant up-regulation of cytochrome P450 Cyp3a11, testosterone oxidation and androgen receptor expression in mouse brain after xenobiotic treatment.
2009 Apr
The use of antipsychotic and anticholinergic antiparkinson drugs in Norway after the withdrawal of orphenadrine.
2009 Aug
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
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
The first asymmetric halogen/metal-exchange reaction: desymmetrization of alcohols with enantiotopic bromoarene substituents.
2009 Jul 6
Influence of orphenadrine upon the protective activity of various antiepileptics in the maximal electroshock-induced convulsions in mice.
2009 Jul-Aug
Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders.
2009 Jun 3
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 Mar
Determination of orphenadrine plasma levels using HPLC with diode array detection and a novel solid-phase extraction procedure in psychiatric patients.
2009 Oct 15
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
Testosterone hydroxylation in bovine liver: enzyme kinetic and inhibition study.
2010 Apr
Comprehensive identification of active compounds in tablets by flow-injection data-dependent tandem mass spectrometry combined with library search.
2010 Apr 15
Orphenadrinium picrate.
2010 Dec 18
Orphenadrinium picrate picric acid.
2010 Feb 24
(2-Methyl-phen-yl)(phen-yl)methanol.
2010 Jul 31
Pharmacologic management of chronic pain.
2010 Jun
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
Full recovery from a potentially lethal dose of orphenadrine ingestion using conservative treatment: a case report.
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

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
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.
Name Type Language
ORPHENADRINE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
ORPHENADRIN
Common Name English
ORPHENADRINE [HSDB]
Common Name English
ORPHENADRINE [MI]
Common Name English
(±)-N,N-DIMETHYL-2-((O-METHYL-.ALPHA.-PHENYLBENZYL)OXY)ETHYLAMINE
Common Name English
orphenadrine [INN]
Common Name English
Orphenadrine [WHO-DD]
Common Name English
ETHANAMINE, N,N-DIMETHYL-2-((2-METHYLPHENYL)PHENYLMETHOXY)-, (±)-
Systematic Name English
MEFENAMINE [JAN]
Common Name English
ORPHENADRINE [VANDF]
Common Name English
MIALGIN
Brand Name English
MEFENAMINE
JAN  
Common Name English
Classification Tree Code System Code
WHO-ATC M03BC51
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
WHO-ATC N04AB02
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
WHO-VATC QM03BC01
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
WHO-VATC QM03BC51
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
NCI_THESAURUS C29704
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
LIVERTOX NBK548850
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
NDF-RT N0000175737
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
NDF-RT N0000175730
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
WHO-ATC M03BC01
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
NCI_THESAURUS C29696
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
Code System Code Type Description
DAILYMED
AL805O9OG9
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
SMS_ID
100000092125
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
CAS
83-98-7
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
EVMPD
SUB09471MIG
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
LACTMED
Orphenadrine
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
ChEMBL
CHEMBL900
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
NCI_THESAURUS
C61868
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
DRUG BANK
DB01173
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
FDA UNII
AL805O9OG9
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
RXCUI
7715
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY RxNorm
EPA CompTox
DTXSID3023396
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
WIKIPEDIA
ORPHENADRINE
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
IUPHAR
7251
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
MERCK INDEX
m8245
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY Merck Index
PUBCHEM
4601
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
DRUG CENTRAL
1999
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
CHEBI
7789
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
HSDB
3139
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
ECHA (EC/EINECS)
201-509-2
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
MESH
D009966
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
INN
658
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY
CHEBI
31984
Created by admin on Fri Dec 15 16:06:49 UTC 2023 , Edited by admin on Fri Dec 15 16:06:49 UTC 2023
PRIMARY