Orphenadrine

Absorption

Orphenadrine is almost completely absorbed in the gastrointestinal tract.

Toxicity

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

Originator

Norflex,Riker,US,1959

The Uses of Orphenadrine

Relaxant (skeletal muscle); antihistaminic.

Background

A muscarinic antagonist used to treat drug-induced parkinsonism and to relieve pain from muscle spasm.

Indications

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

Definition

ChEBI: A tertiary amino compound which is the phenyl-o-tolylmethyl ether of 2-(dimethylamino)ethanol.

Manufacturing Process

As described in US Patent 2,567,351, o-methylbenzhydryl bromide is added slowly to β-dimethylaminoethanol at refluxing temperature. After the addition has been completed the mixture is refluxed and stirred for an additional 16 hours. The mixture is cooled and the bottom layer consisting of the crude hydrobromide salt of β-dimethylaminoethanol is drawn off. The excess amino alcohol is distilled from the upper layer in vacuo and the residue is reacted with citric acid.

brand name

Norflex (3M Pharmaceuticals).

Therapeutic Function

Muscle relaxant

Pharmacokinetics

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.

Enzyme inhibitor

This muscle relaxant and antihistaminic agent (FWfree-base = 269.39 g/mol; CAS 83-98-7) is both a muscarinic and histamine H1 receptor antagonist that also inhibits some cytochrome P450 systems. Classified as an anticholinergic drug (with 58% as potent as atropine) and an ethanolamineclass antihistamine, it also inhibits the noradrenergic transporter and NMDA receptor ion channel (Ki ≈ 6 μM). Commercially available as either the hydrochloride or citrate salt, orphenadrines used to relieve pain of muscle injuries, such as strains and sprains. Target(s): aldehyde oxidase; CYP1A2; CYP2A6; CYP3A4; CYP2B; CYP2B6; CYP2C9; CYP2C19; CYP2D6; histamine H1 receptor; N-methyl-D-aspartate (NMDA) receptor; muscarinic receptor; noradrenaline reuptake.

Metabolism

Biotransformation occurs mainly in the liver. Pharmacologically active metabolites are N-demethyl orphenadrine and N,N-didemethyl orphenadrine.