indication

For use in the treatment of Parkinson's disease and also used to control severe reactions to certain medicines such as reserpine.

pharmacology

Ethopropazine, 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, ethopropazine — because of its anticholinergic action — is largely devoid of neurotoxic side effects. Ethopropazine also has a slight antihistaminic and local anesthetic effect.

mechanism of action

Ethopropazine's antiparkinson action can be attributed to its anticholinergic properties. Ethopropazine partially blocks central (striatal) cholinergic receptors, thereby helping to balance cholinergic and dopaminergic activity in the basal ganglia; salivation may be decreased, and smooth muscle may be relaxed. Drug-induced extrapyramidal symptoms and those due to parkinsonism may be relieved, but tardive dyskinesia is not alleviated and may be aggravated by anticholinergic effects. Ethopropazine's local anesthetic effect is due to its antagonism of the NMDA glutamate receptor. Glutamate is recognized as an important transmitter in nociceptive pathways, and the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, in particular, has been implicated in the mediation of neuropathic pain. Excessive release of glutamate at NMDA receptors on dorsal horn neurons of the spinal cord results in hyperactivation and hypersensitivity of these receptors (perceived as hyperalgesia), thought to be an integral feature of neuropathic pain.

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.

absorption

Well-absorbed from the gastrointestinal tract.

half life

1 to 2 hours

drug interactions

Bromocriptine: The phenothiazine decreases the effect of bromocriptine

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Dexfenfluramine: Decreased anorexic effect, may increase psychotic symptoms

Diethylpropion: Decreased anorexic effect, may increase psychotic symptoms

Donepezil: Possible antagonism of action

Fenfluramine: Decreased anorexic effect, may increase psychotic symptoms

Galantamine: Possible antagonism of action

Guanethidine: Ethopropazine may decrease the effect of guanethidine.

Haloperidol: The anticholinergic increases the risk of psychosis and tardive dyskinesia

Mazindol: Decreased anorexic effect, may increase psychotic symptoms

Phentermine: Decreased anorexic effect, may increase psychotic symptoms

Phenylpropanolamine: Decreased anorexic effect, may increase psychotic symptoms