ETHOPROPAZINE

Absorption

Well-absorbed from the gastrointestinal tract.

Toxicity

Symptoms of overdose include severe clumsiness or unsteadiness, severe drowsiness, severe dryness of mouth, nose, or throat, fast heartbeat, shortness of breath or troubled breathing, and warmth, dryness, and flushing of skin.

Originator

Parsidol,Warner Lambert,US,1954

The Uses of ETHOPROPAZINE

antiparkinsonian, anticholinergic

Indications

Profenamine is indicated in the symptomatic treatment of drug-induced extrapyramidal reactions and of the manifestations (rigidity, akinesia, sialorrhea, oculogyric crisis, tremor, etc.) of Parkinson's disease of encephalitic, arteriosclerotic or idiopathic origin. It is also used to control severe reactions to certain medicines such as reserpine.

Background

Profenamine (also known as ethopropazine) is a medication derived from phenothiazine. It is primarily used as an antidyskinetic to treat Parkinsonism. It is sold under the trade name Parsitan in Canada. In the US, the marketing of profenamine has been discontinued.

Definition

ChEBI: A member of the class of phenothiazines that is phenothiazine in which the hydrogen attached to the nitrogen is substituted by a 2-(diethylamino)propyl group. An antimuscarinic, it is used as the hydrochloride for the symptomatic treatment of Parkinson's d sease.

Manufacturing Process

6.2 grams of phenthiazine in 100 cc of warm dry benzene was added during 1 hour with stirring, and in an atmosphere of hydrogen, to the Grignard reagent prepared from 1 gram of magnesium, 6.2 grams of methyl iodide, and 20 cc of dry ether. After boiling for 30 minutes, a solution of 6.6 grams of 2-chloro- 1-diethylamino propane in 10 cc of dry benzene was added during 1 hour to the boiling solution, and heating was maintained for a further 1.5 hours.
The reaction mixture was then cooled and treated with aqueous ammonium chloride and chloroform added to dissolve an oil at the interface of the benzene and aqueous layers. The chloroform-benzene extract was extracted with 2 N hydrochloric acid and the acid extract was basified at 5° to 10°C with 50% aqueous sodium hydroxide.
There was obtained a mixture of N-(2'-diethylamino-2'- methylethyl)phenthiazine and N-(2'-diethylamino-1'-methylethyl)phenthiazine in the form of a viscous yellow oil, BP 202° to 205°C/2 mm. This oil was treated in ethereal solution with ethereal hydrogen chloride and gave a white solid which was fractionally crystallized from ethylene dichloride. The less soluble fraction, N-(2'-diethylamino-2'-methylethyl)phenthiazine hydrochloride formed colorless rhombs, MP 223° to 225°C. The more soluble N-(2'- diethylamino-1'-methylethyl)phenthiazine hydrochloride was obtained as colorless prismatic needles, MP 166° to 168°C.

Therapeutic Function

Antiparkinsonian

Pharmacokinetics

Profenamine, a phenothiazine and antidyskinetic, is used in the treatment of Parkinson's disease. By improving muscle control and reducing stiffness, this drug permits more normal movements of the body as the disease symptoms are reduced. It is also used to control severe reactions to certain medicines such as reserpine, phenothiazines, chlorprothixene, thiothixene, loxapine, and haloperidol. Unlike other NMDA antagonists, profenamine — because of its anticholinergic action — is largely devoid of neurotoxic side effects. Profenamine also has a slight antihistaminic and local anesthetic effect.

Safety Profile

Poison by ingestion, subcutaneous, and intravenous routes. An anticholinergic agent used to treat Parkinson's dsease. When heated to decomposition it emits very toxic fumes of NOx and SOx.

Metabolism

Not Available