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

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
Structure of ORPHENADRINE CITRATE

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)

HIDE SMILES / InChI

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 ( + / - )

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class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs.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
[Diagnostic image (17). Acute dystonia induced by prochlorperazine].
2000 Dec 23
In vitro long-term cytotoxicity testing of 27 MEIC chemicals on Hep G2 cells and comparison with acute human toxicity data.
2001 Apr
Orphenadrine prevents 3-nitropropionic acid-induced neurotoxicity in vitro and in vivo.
2001 Feb
Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes.
2001 Jun
Involvement of human liver cytochrome P4502B6 in the metabolism of propofol.
2001 Mar
[Experience gained with the drug amizon in the treatment of patients with mumps, with special reference to its effects on some biochemical markers].
2001 Mar-Apr
Metabolism of territrem a in liver microsomes from male wistar rats: 3. Cytochrome p-450 isoforms catalyzing tra metabolism.
2002 Dec 27
Anticholinergics for symptomatic management of Parkinson's disease.
2003
Therapeutic response of benzodiazepine, orphenadrine citrate and occlusal splint association in TMD pain.
2003 Apr
Affinity and specificity of N-methyl- D-aspartate channel blockers affect their ability to disrupt prepulse inhibition of acoustic startle in rats.
2003 Feb
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Neuronal sensitization and its behavioral correlates in a rat model of neuropathy are prevented by a cyclic analog of orphenadrine.
2003 Jun
Upregulation of cytochromes P450 2B in rat liver by orphenadrine.
2003 Jun
Cytochrome P-4503A1 catalyzes the formation of MA1 from territrem a in liver microsomes of 7-week-old female Wistar rats.
2003 Mar 14
Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats.
2003 Nov
300-Hz subthalamic oscillations in Parkinson's disease.
2003 Oct
[Diclofenac 75mg. and 30 mg. orfenadine (Neodolpasse) versus placebo and piroxicam in postoperative analgesia after arthroscopy].
2004
Alternatives to levodopa in the initial treatment of early Parkinson's disease.
2005
[Comparative study between botulin toxin and bupivacaine for triggering-points infiltration in chronic myofascial syndrome.].
2005 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
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
Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery.
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
Evaluation of enantioselective binding of antihistamines to human serum albumin by ACE.
2007 Aug
Parkinson's disease and dopaminergic therapy--differential effects on movement, reward and cognition.
2008 Aug
Effect of warnings in a medical journal on the use of orphenadrine.
2008 Aug
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
The first asymmetric halogen/metal-exchange reaction: desymmetrization of alcohols with enantiotopic bromoarene substituents.
2009 Jul 6
Determination of orphenadrine plasma levels using HPLC with diode array detection and a novel solid-phase extraction procedure in psychiatric patients.
2009 Oct 15
Orphenadrinium picrate.
2010 Dec 18
Orphenadrinium picrate picric acid.
2010 Feb 24
(2-Methyl-phen-yl)(phen-yl)methanol.
2010 Jul 31
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 Dec 15 17:06:08 UTC 2023
Edited
by admin
on Fri Dec 15 17:06:08 UTC 2023
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
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 [VANDF]
Common Name English
INVAGESIC COMPONENT ORPHENADRINE CITRATE
Common Name English
NSC-757238
Code English
ORPHENADRINE CITRATE [USP MONOGRAPH]
Common Name English
Orphenadrine citrate [WHO-DD]
Common Name 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 [EP IMPURITY]
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 Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
NCI_THESAURUS C29696
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
Code System Code Type Description
ECHA (EC/EINECS)
225-137-5
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
DRUG BANK
DBSALT000400
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
DAILYMED
X0A40N8I4S
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
CHEBI
7790
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
SMS_ID
100000092072
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
RXCUI
7716
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY RxNorm
ChEMBL
CHEMBL900
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
PUBCHEM
20846
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
NCI_THESAURUS
C47641
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
CAS
4724-58-7
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
NON-SPECIFIC STOICHIOMETRY
RS_ITEM_NUM
1479009
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
CAS
4682-36-4
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
MERCK INDEX
m8245
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY Merck Index
EPA CompTox
DTXSID8044678
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
EVMPD
SUB03546MIG
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
FDA UNII
X0A40N8I4S
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
NSC
757238
Created by admin on Fri Dec 15 17:06:08 UTC 2023 , Edited by admin on Fri Dec 15 17:06:08 UTC 2023
PRIMARY
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