Thioridazine

Overview

Thioridazine (sold under the brand names Mellaril or Melleril) is a first-generation antipsychotic drug belonging to the phenothiazine drug group. It 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 The branded product was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias.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 still available in the United States.[1] WP

Risks and side effects

Side effects

Thioridazine prolongs the QTc interval in a dose-dependent manner. It produces significantly less extrapyramidal side effects than most first-generation antipsychotics, likely due to its potent anticholinergic effect. Its use, along with the use of other typical antipsychotics, has been associated with degenerative retinopathies (specifically retinitis pigmentosa). 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. Thioridazine is also associated with abnormal retinal pigmentation after many years of use. Thioridazine has been correlated to rare instances of clinically apparent acute cholestatic liver injury.[2–9] WP

Pharmacology

Pharmacology

Thioridazine has the following binding profile:[10] WP⚠ A table follows this text in the source and is not copied here. Open the source to see it.

Note: The Binding affinities given are towards cloned human receptors unless otherwise specified WP

Acronyms used HB – Human brain receptor RC – Cloned rat receptor ND – No data WP

History

History

Thioridazine was first synthesized in 1958 by Swiss pharmaceutical company Sandoz. It quickly entered widespread clinical use, as there were few alternatives for treating schizophrenia. In 2005, thioridazine was voluntarily discontinued by its manufacturer, Novartis, worldwide because it caused severe cardiac arrhythmias. However, generics remain on the market in some countries. Generic forms of thioridazine however remain on the market in a few countries, usually with restrictions. For example, in the US it is restricted to patients who have taken at least 2 other antipsychotics that either failed or caused serious side effects.[1][11–15] WP

Chemistry

Formula

C21H26N2S2 PC

CAS number

50-52-2 PC

Molar mass (g/mol)

370.6 PC

IUPAC name (computed by PubChem)

10-[2-(1-methylpiperidin-2-yl)ethyl]-2-methylsulfanylphenothiazine PC

SMILES

CN1CCCCC1CCN2C3=CC=CC=C3SC4=C2C=C(C=C4)SC PC

InChIKey

KLBQZWRITKRQQV-UHFFFAOYSA-N PC

PubChem CID

5452

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other SHARED CARE PROTOCOL Thioridazine. March 2012
2. Journal / agency THIORIDAZINE HYDROCHLORIDE tablet, film coated [Mutual Pharmaceutical]. September 2010
3. Journal / agency Fenton M, Rathbone J, Reilly J, Sultana A. Thioridazine for schizophrenia. The Cochrane Database of Systematic Reviews. July 2007. doi:10.1002/14651858.CD001944.pub2 · PMID 17636691 · PMC6718212
4. Journal / agency Keks N, McGrath J, Lambert T, Catts S, Vaddadi K, Burrows G, Varghese F, George T, Hustig H, Burnett P. The Australian multicentre double-blind comparative study of remoxipride and thioridazine in schizophrenia. Acta Psychiatrica Scandinavica. November 1994. doi:10.1111/j.1600-0447.1994.tb01607.x · PMID 7872041
5. Journal / agency Fornaro P, Calabria G, Corallo G, Picotti GB. Pathogenesis of degenerative retinopathies induced by thioridazine and other antipsychotics: a dopamine hypothesis. Documenta Ophthalmologica. Advances in Ophthalmology. July 2002. doi:10.1023/A:1015768114192 · PMID 12152801
6. Other Martindale: The Complete Drug Reference. 18 August 2010
7. Other Selected adverse effects of antipsychotic medications for schizophrenia
8. Journal / agency Scott AW. Retinal Pigmentation in a Patient Receiving Thioridazine. Archives of Ophthalmology. December 1963. doi:10.1001/archopht.1963.00960050777009 · PMID 14065014
9. Journal / agency LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012. PMID 31643669
10. Other Roth BL, Driscol J. PDSP Kᵢ Database. 12 January 2011
11. Other Abdel-Moety EM, Al-Rashood KA. Analytical profiles of drug substances. 1989
12. Journal / agency Purhonen M, Koponen H, Tiihonen J, Tanskanen A. Outcome of patients after market withdrawal of thioridazine: a retrospective analysis in a nationwide cohort. Pharmacoepidemiology and Drug Safety. November 2012. doi:10.1002/pds.3346 · PMID 22941581
13. Journal / agency WHO Pharmaceuticals Newsletter 2005, No. 04: REGULATORY MATTERS: Thioridazine - Sale discontinued in Canada. 2005
14. Journal / agency Withdrawal of thioridazine. Australian Prescriber. June 2007
15. Journal / agency Thioridazine: MedlinePlus Drug Information

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.