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Details

Stereochemistry RACEMIC
Molecular Formula C18H23NO.C6H8O7
Molecular Weight 461.5058
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ORPHENADRINE CITRATE

SMILES

Cc1ccccc1C(c2ccccc2)OCCN(C)C.C(C(=O)O)C(CC(=O)O)(C(=O)O)O

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)

HIDE SMILES / InChI

Molecular Formula C6H8O7
Molecular Weight 192.1238
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C18H23NO
Molecular Weight 269.382
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs.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
[Pilot study on the effects of an antiparkinson anticholinergic agent during depressive conditions].
1975
Prochlorperazine in childhood: side-effects.
1977
Reversal of orphenadrine-induced ventricular tachycardia with physostigmine.
1991 Nov-Dec
Non-sustained ventricular tachycardia due to low-dose orphenadrine.
2001 Oct 1
Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity.
2002
Metabolism of territrem a in liver microsomes from male wistar rats: 3. Cytochrome p-450 isoforms catalyzing tra metabolism.
2002 Dec 27
Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes.
2002 Jul
Therapeutic response of benzodiazepine, orphenadrine citrate and occlusal splint association in TMD pain.
2003 Apr
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.
2003 Nov 17
Analgesic effects of low-dose intravenous orphenadrine in the state of capsaicin hyperalgesia. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from capsaicin-irritated skin in healthy volunteers.
2004
Objective high-frequency tinnitus of middle-ear myoclonus.
2004 Mar
Primary chemotherapy with gemcitabine, epirubicin and taxol (GET) in operable breast cancer: a phase II study.
2005 Aug 22
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
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
Restless legs syndrome: diagnosis and review of management options.
2006 Jun
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
Anticholinergic drug-induced delirium in an elderly Alzheimer's dementia patient.
2007
Characterization of antihistamine-human serum protein interactions by capillary electrophoresis.
2007 Apr 20
Evaluation of enantioselective binding of antihistamines to human serum albumin 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
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
Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration.
2008 Dec
Genetic and chemical modifiers of a CUG toxicity model in Drosophila.
2008 Feb 13
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 Jan
[Diclofenac/orphenadrine as a combined analgetic in post-operative relief of pain].
2008 Sep 28
Demographics of toxic exposures presenting to three public hospital emergency departments in Singapore 2001-2003.
2009 Apr
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
The first asymmetric halogen/metal-exchange reaction: desymmetrization of alcohols with enantiotopic bromoarene substituents.
2009 Jul 6
Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders.
2009 Jun 3
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
Orphenadrinium picrate.
2010 Dec 18
Orphenadrinium picrate picric acid.
2010 Feb 24
(2-Methyl-phen-yl)(phen-yl)methanol.
2010 Jul 31
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

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.
Substance Class Chemical
Created
by admin
on Fri Jun 25 20:45:55 UTC 2021
Edited
by admin
on Fri Jun 25 20:45:55 UTC 2021
Record UNII
X0A40N8I4S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ORPHENADRINE CITRATE
EP   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
Common Name English
ORPHENADRINE CITRATE COMPONENT OF ORPHENGESIC
Common Name English
ORPHENADRINE DIHYDROGEN CITRATE
Common Name English
ORPHENADRINE CITRATE COMPONENT OF INVAGESIC FORTE
Common Name English
ORPHENADRINE CITRATE [EP]
Common Name English
ORPHENADRINE CITRATE [WHO-DD]
Common Name English
ORPHENGESIC FORTE COMPONENT ORPHENADRINE CITRATE
Common Name English
NORFLEX
Brand Name English
(+/-)-N,N-DIMETHYL-2-((O-METHYL-.ALPHA.-PHENYLBENZYL)OXY)ETHYLAMINE CITRATE (1:1)
Common Name English
INVAGESIC FORTE COMPONENT ORPHENADRINE CITRATE
Common Name English
ORPHENADRINE CITRATE [ORANGE BOOK]
Common Name English
ORPHENADRINE CITRATE [MART.]
Common Name English
ORPHENADRINE CITRATE COMPONENT OF NORGESIC
Common Name English
ORPHENADRINE CITRATE [EP MONOGRAPH]
Common Name English
ORPHENGESIC COMPONENT ORPHENADRINE CITRATE
Common Name English
ORPHENADRINE CITRATE [MI]
Common Name English
ORPHENADRINE CITRATE [USP]
Common Name English
ORPHENADRINE CITRATE [VANDF]
Common Name English
INVAGESIC COMPONENT ORPHENADRINE CITRATE
Common Name English
NSC-757238
Code English
ETHANAMINE, N,N-DIMETHYL-2-((2-METHYLPHENYL)PHENYLMETHOXY)-, (+/-)-, 2-HYDROXY-1,2,3-PROPANETRICARBOXYLATE (1:1)
Systematic Name English
ORPHENADRINE CITRATE COMPONENT OF ORPHENGESIC FORTE
Common Name English
ORPHENADRINE CITRATE COMPONENT OF INVAGESIC
Common Name English
BANFLEX
Common Name English
NORGESIC COMPONENT ORPHENADRINE CITRATE
Common Name English
Classification Tree Code System Code
WHO-ATC M03BC01
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
NCI_THESAURUS C29696
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
Code System Code Type Description
ECHA (EC/EINECS)
225-137-5
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY
DRUG BANK
DBSALT000400
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY
RXCUI
7716
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL900
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY
PUBCHEM
20846
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY
USP_CATALOG
1479009
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY USP-RS
NCI_THESAURUS
C47641
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY
CAS
4724-58-7
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
NON-SPECIFIC STOICHIOMETRY
CAS
4682-36-4
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY
MERCK INDEX
M8245
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY Merck Index
EPA CompTox
4682-36-4
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY
EVMPD
SUB03546MIG
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY
FDA UNII
X0A40N8I4S
Created by admin on Fri Jun 25 20:45:55 UTC 2021 , Edited by admin on Fri Jun 25 20:45:55 UTC 2021
PRIMARY
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