indication

Used in the treatment of schizophrenia, organic brain disorders, alcoholism and psychoneuroses.

pharmacology

Mesoridazine, the besylate salt of a metabolite of thioridazine, is a phenothiazine tranquilizer. Pharmacological studies in laboratory animals have established that mesoridazine has a spectrum of pharmacodynamic actions typical of a major tranquilizer. In common with other tranquilizers it inhibits spontaneous motor activity in mice, prolongs thiopental and hexobarbital sleeping time in mice and produces spindles and block of arousal reaction in the EEG of rabbits. It is effective in blocking spinal reflexes in the cut and antagonizes d-amphetamine excitation and toxicity in grouped mice. It shows a moderate adrenergic blocking activity in vitro and in vivo and antagonizes 5-hydroxytryptamine in vivo. Intravenously administered, it lowers the blood pressure of anesthetized dogs. It has a weak antiacetylcholine effect in vitro.

mechanism of action

Based upon animal studies, mesoridazine, as with other phenothiazines, acts indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced without affecting its intrinsic ability to activate the cerebral cortex. In addition, the phenothiazines exhibit at least part of their activities through depression of hypothalamic centers. Neurochemically, the phenothiazines are thought to exert their effects by a central adrenergic blocking action.

toxicity

Oral LD₅₀ is 560 ± 62.5 mg/kg and 644 ± 48 mg/kg in mouse and rat, respectively. Symptoms of overdose may include emesis, muscle tremors, decreased food intake and death associated with aspiration of oral-gastric contents into the respiratory system.

absorption

Well absorbed from the gastrointestinal tract.

half life

24 to 48 hours

drug interactions

Amiodarone: Increased risk of cardiotoxicity and arrhythmias

Amitriptyline: Increased risk of cardiotoxicity and arrhythmias

Amphetamine: Decreased anorexic effect, may increase psychotic symptoms

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Benzphetamine: Antipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.

Bretylium: Increased risk of cardiotoxicity and arrhythmias

Bromocriptine: The phenothiazine decreases the effect of bromocriptine

Chloroquine: Increased risk of cardiotoxicity and arrhythmias

Chlorpromazine: Increased risk of cardiotoxicity and arrhythmias

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Dexfenfluramine: Decreased anorexic effect, may increase psychotic symptoms

Dextroamphetamine: Decreased anorexic effect, may increase psychotic symptoms

Diethylpropion: Decreased anorexic effect, may increase psychotic symptoms

Diltiazem: Increased risk of cardiotoxicity and arrhythmias

Diphenhydramine: Increased risk of cardiotoxicity and arrhythmias

Disopyramide: Increased risk of cardiotoxicity and arrhythmias

Dofetilide: Increased risk of cardiotoxicity and arrhythmias

Donepezil: Possible antagonism of action

Doxepin: Increased risk of cardiotoxicity and arrhythmias

Erythromycin: Increased risk of cardiotoxicity and arrhythmias

Fenfluramine: Decreased anorexic effect, may increase psychotic symptoms

Flecainide: Increased risk of cardiotoxicity and arrhythmias

Fluoxetine: Increased risk of cardiotoxicity and arrhythmias

Fluvoxamine: Increased risk of cardiotoxicity and arrhythmias

Galantamine: Possible antagonism of action

Gatifloxacin: Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Guanethidine: Mesoridazine may decrease the effect of guanethidine.

Halofantrine: Increased risk of cardiotoxicity and arrhythmias

Haloperidol: Increased risk of cardiotoxicity and arrhythmias

Imipramine: Increased risk of cardiotoxicity and arrhythmias

Josamycin: Increased risk of cardiotoxicity and arrhythmias

Levofloxacin: Increased risk of cardiotoxicity and arrhythmias

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Maprotiline: Increased risk of cardiotoxicity and arrhythmias

Mazindol: Decreased anorexic effect, may increase psychotic symptoms

Methamphetamine: Decreased anorexic effect, may increase psychotic symptoms

Metrizamide: Increased risk of cardiotoxicity and arrhythmias

Paroxetine: Increased risk of cardiotoxicity and arrhythmias

Penicillin G: Increased risk of cardiotoxicity and arrhythmias

Pentamidine: Increased risk of cardiotoxicity and arrhythmias

Phendimetrazine: Decreased anorexic effect, may increase psychotic symptoms

Phenmetrazine: Decreased anorexic effect, may increase psychotic symptoms

Phentermine: Decreased anorexic effect, may increase psychotic symptoms

Phenylpropanolamine: Decreased anorexic effect, may increase psychotic symptoms

Pimozide: Increased risk of cardiotoxicity and arrhythmias

Pindolol: Increased risk of cardiotoxicity and arrhythmias

Procainamide: Increased risk of cardiotoxicity and arrhythmias

Propafenone: Increased risk of cardiotoxicity and arrhythmias.

Propranolol: Increased risk of cardiotoxicity and arrhythmias

Quinidine: Increased risk of cardiotoxicity and arrhythmias

Quinidine barbiturate: Increased risk of cardiotoxicity and arrhythmias

Quinine: Increased risk of cardiotoxicity and arrhythmias

Rivastigmine: Possible antagonism of action

Sertindole: Increased risk of cardiotoxicity and arrhythmias

Sotalol: Increased risk of cardiotoxicity and arrhythmias

Sparfloxacin: Increased risk of cardiotoxicity and arrhythmias

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Mesoridazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Tetrabenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Trimethobenzamide: Trimethobenzamide and Mesoridazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Triprolidine: The antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Mesoridazine. Monitor for symptoms of ventricular arrhythmias. Additive anticholinergic and CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Mesoridazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Voriconazole: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).