Orphenadrin

172.5 Ų [M+Na]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: TOXCAST; Source Identifier: DTXSID5025815]

169.51 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

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.

...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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

orphenadrine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

IT...APPEARS THAT IMMATURE RATS ARE.../SOMETIMES/ MORE RESPONSIVE TO ENZYME INDUCTION. THIS IS PARTICULARLY APPARENT FOR ORPHENADRINE...WHICH, ALTHOUGH CAUSING SIGNIFICANT ENZYME INDUCTION IN YOUNG RATS.../IS/ WITHOUT EFFECT IN OLDER ANIMALS.

Orphenadrine

4.7

19.7

For adults, dosage is two 100-mg orphenadrine citrate tablets per day; one in the morning and one in the evening.

Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 200 mg/day, Lowest Therapeutic Dose (LTD): 2.5 mg/kg-day, and Screening Dose: 0.0008 mg/kg-day.

24-Apr-18

AL805O9OG9

ORPHENADRINE

Physiologic Effects [PE] - Centrally-mediated Muscle Relaxation

Established Pharmacologic Class [EPC] - Muscle Relaxant

Orphenadrine is a Muscle Relaxant. The physiologic effect of orphenadrine is by means of Centrally-mediated Muscle Relaxation.

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.

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)

Agents that inhibit the actions of the parasympathetic nervous system. The major group of drugs used therapeutically for this purpose is the MUSCARINIC ANTAGONISTS.

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.

Drugs and compounds which inhibit or antagonize the biosynthesis or actions of CYTOCHROME P-450 CYP2B6.

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/