(±)-Orphenadrine

269.38

269.38

201-509-2

DTXSID3023396

LIQUID

2922199090

12.5

3.6

Solid

1.0278 (rough estimate)

<25 °C

195 °C

1.5740 (estimate)

Sparingly soluble in water

LD50 oral in mouse: 125mg/kg

8.91None

8.91

SPARINGLY SOL IN WATER, SLIGHTLY SOL IN ETHANOL; INSOL IN CHLOROFORM, DIETHYL ETHER & BENZENE; VERY SLIGHTLY SOL IN ACETONE; MP: 136 DEC C /CITRATE/

III

6.1(b)

1851

ORPHENADRINE BASE PPT FROM AQ ALKALINE SOLN

P264, P270, P301+P310, P321, P330, P405, P501

H301

|Danger|H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P301+P310, P321, P330, P405, and P501|Aggregated GHS information provided by 39 companies from 1 notifications to the ECHA C&L Inventory.

Oral, mouse LD50 = 100 mg/kg; oral, rat LD50 = 255 mg/kg

Despite its long clinical use, there is no evidence of hepatotoxicity with orphenadrine. Several cases of severe orphenadrine overdose with cardio-respiratory arrest and ischemic hepatic injury have been reported. Conventional doses of orphenadrine appear to be free of hepatic injury.

ORPHENADRINE HAS BEEN REPORTED TO ENHANCE CNS EFFECTS OF PROPOXYPHENE WHEN THESE DRUGS ARE USED CONCURRENTLY.|IN MICE BOTH NEOSTIGMINE & PHYSOSTIGMINE INCREASED TOXICITY OF ORPHENADRINE. BUT ARECOLINE...PROVIDED SIGNIFICANT PROTECTION AGAINST ACUTE LETHAL EFFECTS.

95%

Indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculo skeletal conditions.|FDA Label

Orphenadrine is a centrally acting muscle relaxant that has been in clinical use for more than 50 years and has not been linked to liver injury or clinically apparent drug induced liver disease.

Autonomic Agents: Muscle Relaxants, Central

Antiparkinson Agents; Muscarinic Antagonists; Muscle Relaxants, Central; Parasympatholytics|ANTIHISTAMINE WHICH REDUCES VOLUNTARY MUSCLE SPASM... IT IS USED IN SYMPTOMATIC MGMNT OF PARKINSON'S DISEASE. IN ADDITION TO DECR SPASTICITY, OCULOGYRIA, & BLEPHAROSPASM, IT ALSO MAY REDUCE SIALORRHEA & DIAPHORESIS. ... ALSO IS USED IN MGMNT OF ACUTE SPASTIC DISORDERS OF SKELETAL MUSCLES... /CITRATE/|ALL TYPES OF EXPTL HYPERTONIA & HYPERREFLEXIA, SUCH AS PRODUCED BY DECEREBRATION OR BY SPINAL OR SUPRASPINAL LESIONS ARE DIMINISHED BY NONPARALYZING DOSES... THEY ALSO AFFORD PROTECTION AGAINST CERTAIN CONVULSIVE AGENTS, PARTICULARLY STRYCHNINE, & AGAINST ELECTROSHOCK SEIZURES. /CENTRALLY ACTING MUSCLE RELAXANTS/|...ADMIN IV HAVE ESTABLISHED VALUE IN TREATING ACUTE MUSCLE SPASMS ASSOC WITH TRAUMA & INFLAMMATION. THEY ARE ALSO BENEFICIAL IN PRODUCING MUSCLE RELAXATION FOR CERTAIN ORTHOPEDIC MANIPULATIONS. ...MAY TEMPORARILY ABATE SOME OF SYMPTOMS OF CEREBRAL PALSY... /CENTRALLY ACTING MUSCLE RELAXANTS/|For more Therapeutic Uses (Complete) data for ORPHENADRINE (7 total), please visit the HSDB record page.

...TREMOR MAY BE EXACERBATED. CONSEQUENTLY, DRUG IS USEFUL ONLY AS ADJUNCT TO OTHER THERAPY. /CITRATE/|...IS CONTRAINDICATED IN PT WITH ACUTE-ANGLE CLOSURE GLAUCOMA OR MYASTHENIA GRAVIS. IT SHOULD BE USED CAUTIOUSLY IN PT WITH GI OBSTRUCTION, URINARY RETENTION, URINARY TRACT OBSTRUCTION, OR TACHYCARDIA... /CITRATE/

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 anaesthetic 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 favourable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. The effect is somewhat less on bradykinesia.

Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2B6. (See all compounds classified as Cytochrome P-450 CYP2B6 Inhibitors.)|A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358) (See all compounds classified as Muscle Relaxants, Central.)|Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists. (See all compounds classified as Antiparkinson Agents.)|Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. (See all compounds classified as Muscarinic Antagonists.)|Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS. (See all compounds classified as Parasympatholytics.)

Orphenadrine is almost completely absorbed in the gastrointestinal tract.|H-3-ORPHENADRINE CITRATE APPEARED TO BE EQUIAVAILABLE TO TISSUES OF MAN FROM CAPSULE & TABLET DOSAGE FORMS. SIXFOLD MORE (3)H WAS EXCRETED, RELATIVELY SLOWLY, IN URINE THAN IN FECES, POSSIBLY OWING TO SLOW TISSUE RELEASE OF (3)H OR TO ENTEROHEPATIC CIRCULATION. /CITRATE/|ELIMINATION T/2'S OF ORPHENADRINE CITRATE & ITS MAJOR METABOLITES RANGED BETWEEN 14 & 25 HR. /CITRATE/|CONSIDERABLE BILIARY EXCRETION IN RAT HAS BEEN NOTED FOR ORPHENADRINE...|BILIARY EXCRETION OF (14)C- OR (3)H-/ORPHENADRINE/...EXAMINED IN DETAIL. THREEFOLD MORE RADIOACTIVITY...EXCRETED IN BILE AFTER IV DOSE...THAN AFTER ORAL DOSE. ...LIVER CONCN OF RADIOACTIVITY...ONE-HUNDREDFOLD THOSE IN BLOOD, & BILE CONCN...SEVENFOLD THOSE IN LIVER. /CITRATE/

Biotransformation occurs mainly in the liver. Pharmacologically active metabolites are N-demethyl orphenadrine and N,N-didemethyl orphenadrine.|UNLIKE DIPHENHYDRAMINE, ORPHENADRINE IS POWERFUL ANTI-PARKINSON AGENT, & DIFFERENCES IN PHARMACOLOGICAL ACTIVITY MAY BE ATTRIBUTABLE TO DIFFERENT METABOLIC PATHWAYS OF TWO DRUGS & CORRESPONDINGLY SLOWER RATES OF METABOLISM & EXCRETION OF ORPHENADRINE.|BIOTRANSFORMATION IN RATS OF DIPHENHYDRAMINE ANALOGUE ORPHENADRINE...AFFORDED BY OXIDATIVE DEALKYLATION SECONDARY & PRIMARY AMINES...CORRESPONDING TO ORPHENADRINE & O-DEALKYLATION PRODUCT, 2-METHYLBENZHYDROL.|STUDIES...IN MAN HAVE REVEALED...8 EXCRETORY PRODUCTS. BESIDES SECONDARY (8.1% OF DOSE) & PRIMARY AMINES (4.4%)...2-METHYLBENZHYDROL (0.5%)...ORPHENADRINE N-OXIDE (4.6%), GLUCURONIDES (13.0%)...& 2-METHYLBENZHYDRYLOXYACETIC ACID (0.2%) HAVE NOW BEEN IDENTIFIED.|SINCE ORTHO-TOLYLPHENYLMETHYL RESIDUE EXCRETED UNCHANGED IN URINE ACCOUNTS FOR 50% OF DOSE...METABOLISM INVOLVING AROMATIC RING(S) WAS ALSO MAJOR ROUTE FOR ORPHENADRINE. IN...BILIARY SECRETION...IN RATS, PRODUCTS WITH PROPERTIES CORRESPONDING TO 2-CARBOXYDIPHENHYDRAMINE & ITS CONJUGATE WITH GLUTAMINE HAVE BEEN DETECTED.|For more Metabolism/Metabolites (Complete) data for ORPHENADRINE (6 total), please visit the HSDB record page.

13-20 hours

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.|ANTIPARKINSONISM DRUGS ALSO BLOCK CHOLINERGIC RECEPTORS. THEY ARE... ORPHENADRINE (DISIPAL)... BLOCKADE PREVENTS ACTIONS OF ACETYLCHOLINE RELEASED FROM PARASYMPATHETIC NERVE ENDINGS.|...REDUCES VOLUNTARY MUSCLE SPASM BY CENTRAL ANTIMUSCARINIC ACTION & RESEMBLES ATROPINE IN THIS RESPECT. /CITRATE/|NEURONAL CONDUCTION, NEUROMUSCULAR TRANSMISSION, & MUSCLE EXCITABILITY ARE NOT DEPRESSED EXCEPT AFTER NEARLY LETHAL DOSES. PROMINENT EFFECT...IS TO DEPRESS SPINAL POLYSYNAPTIC REFLEXES PREFERENTIALLY OVER MONOSYNAPTIC REFLEXES. /CENTRALLY ACTING MUSCLE RELAXANTS/

...COMMONLY PRODUCE...LETHARGY, ATAXIA, & NYSTAGMUS. ...VOMITING, HEARTBURN, & ABDOMINAL DISTRESS ARE ALSO OBSERVED, ESP AFTER LARGE ORAL DOSES. HYPERSENSITIVITY REACTIONS INCL SKIN RASH & PRURITUS &, RARELY, ANAPHYLACTOID REACTIONS & LEUKOPENIA. /CENTRALLY ACTING MUSCLE RELAXANTS/|...SOMETIMES INDUCES MILD EXCITEMENT & ALSO MILD EUPHORIA IN FATIGUED OR DEPRESSED PT. PERIPHERAL ATROPINE-LIKE ACTIONS ARE WEAK, BUT BLURRED VISION, DRY SKIN, & DRY MOUTH MAY OCCUR. OTHER SIDE EFFECTS INCL NAUSEA, VERTIGO, RASH, HEADACHE, DIZZINESS, DROWSINESS, CONSTIPATION, INCR INTRAOCULAR PRESSURE... /CITRATE/|OTHER SIDE EFFECTS INCL...WEAKNESS, MENTAL CONFUSION, & OCCASIONAL HALLUCINATIONS. /CITRATE/|IN YOUNG CHILDREN DOSES AS LOW AS 600-800 MG HAVE PRODUCED SEVERE INTOXICATIONS & DEATH. AT LEAST 2 ADULTS EXPIRED AFTER INGESTION OF 1 TO 1.5 G, BUT WITH SUPPORTIVE CARE 1 ADULT SURVIVED SEVERE SYMPTOMS PPT BY INGESTION OF 7.5 G.|For more Human Toxicity Excerpts (Complete) data for ORPHENADRINE (6 total), please visit the HSDB record page.

Citrate, Norflex Orphenadrine

INJECTION NF: 60 MG/2 ML; TABLETS: 100 MG. /CITRATE/|MEPHENAMIN /HYDROCHLORIDE/. NORFLEX /CITRATE/.

BY ORAL ROUTE CITRATE & HYDROCHLORIDE ARE EQUALLY EFFICACIOUS, IF ALLOWANCE IN DOSE IS MADE FOR DIFFERENCE IN MOLECULAR WT. MANUFACTURER'S RECOMMENDATIONS OF LONGER INTERVAL BETWEEN DOSES OF CITRATE THAN OF HYDROCHLORIDE IS BASED UPON RETARDING EFFECT OF PLASTICIZED MATRIX IN WHICH ORAL CITRATE IS COMPOUNDED. /CITRATE/

GAS CHROMATOGRAPHIC DETERMINATION OF ORPHENADRINE IN HUMAN BODY FLUIDS.|GAS CHROMATOGRAPHIC DETERMINATION OF ORPHENADRINE IN POSTMORTEM BLOOD USING A NITROGEN PHOSPHORUS DETECTOR.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals