Orphenadrine Citrate

What Is Orphenadrine Citrate?

Orphenadrine citrate (ORPH) is an anticholinergic medical agent. Its most prominent indication is Parkinson’s disease in the treatment of muscle pain and enhancing motor control. Orphenadrine is a muscle-relaxant drug used to treat painful muscle spasm due to soft tissue injuries and Parkinson’s disease. Orphenadrine citrate has a major role as muscle relaxant in numerous disorders. Orphenadrine also shows a nonspecific antagonistic activity at the phencyclidine binding site of the N-methyl-D-aspartate (NMDA) receptor ^.(1) The generic name of orphenadrine citrate is -N,N-Dimethyl-2-[(o-methyl- ⟨-phenylbenzyl)oxy] ethylamine citrate with a molecular formula C18H23NOC6H8O7. Its molecular weight is 461.51.

In regards to its biochemical structure, orphenadrine citrate is the citrate salt of orphenadrine. It is in the form of a white, crystall powder, odorless with a sour taste. It is hydrosoluble and minimally soluble in alcohol. Orphenadrine citrate is a medication used to treat skeletal muscle spasms and belongs to a group of skeletal muscle relaxants. Skeletal muscle relaxants have a depressing effect on the central nervous system with an onset of action between 30 and 60 minutes.

Pharmacology

Orphenadrine is a multitarget inhibitor, including histaminic, muscarinic and N-methyl-D-aspartate (NMDA) receptors, as well as the norepinephrine reuptake system. Its hydrochloride salt was introduced into the market as a medication for Parkinson’s disease, to alleviate Some of the troublesome symptoms of the disease, especially the involuntary resting tremor. On the other hand, its citrate salt is widely accepted as a skeletal muscle relaxant with an excellent antinociceptive effect providing benefits against shoulder, neck and low back pain, as well as acute and chronic painful musculoskeletal conditions. Orphenadrine indirectly reduces muscle pain via central atropine-like effects. It has as well certain euphorigenic and analgesic attributes. Orphenadrine is indicated for short term use. In case of chronic administration, ti must be dosed carefully.

 

The detailed molecular mechanism by which orphenadrine induces analgesia is still unknown but what for sure it is centrally. It may be possible for its antihistaminergic properties and NMDA-receptor inhibition activity, however, the hypothesis of inhibiting the voltage-gated sodium channels has become recently solidified as a strong contributor to the analgesic action of orphenadrine.^(R) Orphenadrine is metabolized through the liver with the involvement of CYP450 enzyme system. It represents a minor substrate and weak inhibitor. Its peak function is within two to four hour and may even last up to six hours. In case an individual suffers from heart failure, tachycardia or cardiac arrhythmias it is necessary to administer orphenadrine carefully in such patients. The application of orphenadrine in older individuals is not recommended due to its anticholinergic activities (constipation, urinary retention and confusion)^.(R)

Indications

Orphenadrine is a skeletal muscle relaxant used for the treatment of painful musculoskeletal conditions such as strains, sprains and other muscle injuries. It is used along with rest and physical therapy.

 

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.

Contraindications

1. Allergies to any present compound in orphenadrine
2. Glaucoma
3. Abdominal or intestinal blockage
4. Stomach ulcer
5. Obstructed bladder
6. Esophageal conditions
7. Enlargement of prostate
8. Myasthenia gravis

Orphenadrine citrate extended-release tablets are contraindicated in patients with glaucoma, pyloric or duodenal obstruction, stenosing peptic ulcers, prostatic hypertrophy or obstruction of the bladder neck, cardio-spasm (mega-esophagus) and myasthenia gravis. Orphenadrine citrate tablets are contraindicated in patients who have demonstrated a previous hypersensitivity to the drug.

Side Effects

Possible side effect of the orphenadrine citrate application include sore mouth, drowsiness, dizziness, irritable stomach, vomiting, constipation, imapired urinating, blurred vision, headache. Disorders ,such as fast or irregular heartbeat, fainting, confusion, hallucinations or skin rash are possible as well.

Adverse Reactions

The majority of adverse reactions of orphenadrine are caused by the antiholinergic function of orphenadrine. They are commonly associated with higher doses. Drynesss of the mouth represents the most common adverse reaction of orphenadrine. If the daily dose is increased, additional adverse effects may occur.

The most common are tachycardia, palpitation, difficulties while urinating, impaired vision, dilatation of pupils, increased ocular pressure, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness, hypersensitivity reactions, pruritus, hallucinations, agitation, tremor, gastric irritation and allergic reactions. In minor percent, certain cases of aplastic anemia have been reported.

Dosage & Administration

Orphenadrine citrate comes in the form of tablets and as an injection for intramuscular or intravenous application.

Overdosage

If overdoses, orphenadrine is toxic in humans due to its antiholinergic mechanism. It has been noted that the minimum lethal dose was 2 to 3 grams for adult individuals. Treatment in overdose is the elimination of gastric content, charcoal at repeated doses, careful monitoring and supportive treatment.

References

1. Czuczwar M. Influence of orphenadrine upon the protective activity of various antiepileptics in the maximal electroshock-induced convulsions in mice.Pharmacol Rep. 2009 Jul-Aug;61(4):732-6.
2. Darwish K. Validated stability-indicating reversed-phase-HPLC method for simultaneous determination of orphenadrine citrate, caffeine and aspirin.Chem Pharm Bull (Tokyo). 2012;60(11):1426-36.
3. Kornhuber J, Parsons CG, Hartmann S, et al. (1995). “Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies”. Journal of Neural Transmission. General Section. 102 (3): 237–46.