MedlinePlus a682119 ATC code N05AC02 (WHO) | Routes of
administration Oral CAS ID 50-52-2 | |
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AHFS/Drugs.com Consumer Drug Information License data US DailyMed: 9c4bedb4-2d59-4fcd-aad7-fce988cd96d8
US FDA: Thioridazine Pregnancy
category AU: C
US: C (Risk not ruled out) | ||
Thioridazine kills cancer stem cells insidermedicine in 60 may 24
Thioridazine (Mellaril or Melleril) is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis; the branded product was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias, however, generic versions are available in the US.
Contents
Thioridazine meaning
Indications
Thioridazine was voluntarily discontinued by its manufacturer, Novartis, worldwide because it caused severe cardiac arrhythmias.
Its primary use in medicine was the treatment of schizophrenia. It was also tried with some success as a treatment for various psychiatric symptoms seen in people with dementia, but chronic use of thioridazine and other anti-psychotics in people with dementia is not recommended.
Side effects
For further information see: Phenothiazine
Thioridazine prolongs the QTc interval in a dose-dependent manner. It produces significantly less extrapyramidal side effects than most first-generation antipsychotics. Its use, along with the use of other typical antipsychotics, has been associated with degenerative retinopathies. It has a higher propensity for causing anticholinergic side effects coupled with a lower propensity for causing extrapyramidal side effects and sedation than chlorpromazine, but also has a higher incidence of hypotension and cardiotoxicity. It is also known to possess a relatively high liability for causing orthostatic hypotension compared to other antipsychotics. Similarly to other first-generation antipsychotics it has a relatively high liability for causing prolactin elevation. It is moderate risk for causing weight gain. As with all antipsychotics thioridazine has been linked to cases of tardive dyskinesia (an often permanent neurological disorder characterised by slow, repetitive, purposeless and involuntary movements, most often of the facial muscles, that is usually brought on by years of continued treatment with antipsychotics, especially the first-generation (or typical) antipsychotics such as thioridazine) and neuroleptic malignant syndrome (a potentially fatal complication of antipsychotic treatment). Blood dyscrasias such as agranulocytosis, leukopenia and neutropenia are possible with thioridazine treatment.
Pharmacology
Thioridazine has the following binding profile:
Note: The Binding affinities given are towards cloned human receptors unless otherwise specified
Acronyms used
HB — Human brain receptor
RC — Cloned rat receptor
ND — No data
Metabolism
Thioridazine is a racemic compound with two enantiomers, both of which are metabolized, according to Eap et al., by CYP2D6 into (S)- and (R)-thioridazine-2-sulfoxide, better known as mesoridazine, and into (S)- and (R)-thioridazine-5-sulfoxide. Mesoridazine is in turn metabolized into sulforidazine. Thioridazine is an inhibitor of CYP1A2 and CYP3A2.
History
The manufacturer Novartis/Sandoz/Wander of the brands of thioridazine, Mellaril in the USA and Canada and Melleril in Europe, discontinued the drug worldwide in June 2005.
Antibiotic activity
Thioridazine is known to kill XDR-TB and to make MRSA sensitive to β-lactam antibiotics. A possible mechanism of action for the drug's antibiotic activity is via the inhibition of bacterial efflux pumps.