indication

For the maintenance treatment of chronic non-agitated schizophrenic patients.

pharmacology

Pipotiazine has actions similar to those of other phenothiazines. Among the different phenothiazine derivatives, it appears to be less sedating and to have a weak propensity for causing hypotension or potentiating the effects of CNS depressants and anesthetics. However, it produces a high incidence of extra pyramidal reactions. It reduces activity of dopamine receptors in the limbic system. Its 5-HT antagonism helps normalize dopamine activity in the cortical regions.

mechanism of action

Pipotiazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).

toxicity

Symptoms of overdose include severe extrapyramidal manifestations, hypotension, lethargy and sedation.

drug interactions

Donepezil: Possible antagonism of action

Galantamine: Possible antagonism of action

Telithromycin: Telithromycin may reduce clearance of Pipotiazine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Pipotiazine if Telithromycin is initiated, discontinued or dose changed.

Terbinafine: Terbinafine may reduce the metabolism and clearance of Pipotiazine. Consider alternate therapy or monitor for therapeutic/adverse effects of Pipotiazine if Terbinafine is initiated, discontinued or dose changed.

Triprolidine: The antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Pipotiazine. Monitor for symptoms of ventricular arrhythmias.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of pipotiazine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of pipotiazine if voriconazole is initiated, discontinued or dose changed.