indication

Used as an adjunct for short term treatment of moderate and severe psychomotor agitation. Also used to treat agitation or restlessness in the elderly.

pharmacology

Promazine belongs to a group of medications known as the phenothiazine antipsychotics. It acts by blocking a variety of receptors in the brain, particularly dopamine receptors. Dopamine is involved in transmitting signals between brain cells. When there is an excess amount of dopamine in the brain it causes over-stimulation of dopamine receptors. These receptors normally act to modify behaviour and over-stimulation may result in psychotic illness. Promazine hydrochloride blocks these receptors and stops them becoming over-stimulated, thereby helping to control psychotic illness. Promazine has weak extrapyramidal and autonomic side effects which lead to its use in the elderly, for restless or psychotic patients. Its anti-psychotic effect is also weaker and it is not useful in general psychiatry.

mechanism of action

Promazine is an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Promazine's antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Promazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone. Antagonism at muscarinic receptors, H1-receptors, and alpha(1)-receptors also occurs with promazine.

toxicity

Side effects include: extrapyramidal symptoms, drowsiness, weight gain, dry mouth, constipation, endocrine effects (such as gynaecomastia and menstrual disturbance), sensitivity to sunlight and haemolytic anaemia.

biotransformation

Hepatic, primarily to N-desmethylpromazine and promazine sulfoxide.

absorption

Absorption may be erratic and peak plasma concentrations show large interindividual differences.

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

Gatifloxacin: Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Guanethidine: Promazine may decrease the effect of guanethidine.

Levofloxacin: Increased risk of cardiotoxicity and arrhythmias

Mazindol: Decreased anorexic effect, may increase psychotic symptoms

Phentermine: Decreased anorexic effect, may increase psychotic symptoms

Phenylpropanolamine: Decreased anorexic effect, may increase psychotic symptoms

Terfenadine: Increased risk of cardiotoxicity and arrhythmias