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Not to be confused with Thorazine.
Systematic (IUPAC) name
Clinical data
AHFS/ Consumer Drug Information
MedlinePlus a682119
Licence data US Daily Med:link
  • AU: C
  • US: C
Pharmacokinetic data
Bioavailability incomplete
Metabolism hepatic (at least partly mediated by CYP2D6)
Half-life 21-24 hours[1]
Excretion faeces
50-52-2 YesY
PubChem CID 5452
IUPHAR ligand 100
DrugBank DB00679 YesY
ChemSpider 5253 YesY
KEGG D00373 YesY
Chemical data
Formula C21H26N2S2
 YesY (what is this?)  (verify)

Thioridazine (Mellaril (DE, BD, ET, ID, BR), Melleril (withdrawn worldwide in 2005[2]), Sonapax (RU), Thioril (IN)) is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. Due to concerns about cardiotoxicity and retinopathy at high doses this drug has been withdrawn in many countries (including the UK and Australia) and in other countries it is not commonly prescribed, reserved for patients who have failed to respond to, or have contraindications for, more widely used antipsychotics.

In older references, it is sometimes described as atypical,[3] but more recently it is usually described as typical,[4] with the term "atypical" usually reserved for agents showing D4 selectivity or serotonin antagonism. The atypicality of second generation agents is not clearly defined. Some believe it's low D2 affinity, quick dissociation, 5-HT2A receptor antagonism, or all of the above. Its perceived atypical effects (namely its comparatively low propensity for extrapyramidal side effects) are likely the result of its potent anticholinergic effects.


Its primary use in medicine is in the treatment of schizophrenia.[5] It has also been tried with some success as a treatment for various psychiatric symptoms seen in patients with dementia.[6]

Thioridazine is known to kill intracellular extensively drug-resistant (XDR) Mycobacterium tuberculosis[7][8] and both inhibit MRSA directly but also increase the susceptibility of MRSA to β-lactam antibiotics at clinical concentrations.[9][10] It also appears to increase the efficacy of standard antimicrobial agents (even ones to which the strain in question is resistant) in treating XDR-tuberculosis (XDR-TB) via inhibiting bacterial efflux pumps.[8]

The product Melleril® has been voluntarily discontinued by its manufacturer, Novartis, worldwide.[11] Consequently it was withdrawn from the UK[2] and Canada in July 2005.[12] Stocks of Melleril ran out in Australia in August 2007.[13]

Side effects[edit]

For further information see: Phenothiazine

Thioridazine prolongs the QTc interval in a dose-dependent manner.[14] It produces significantly less extrapyramidal side effects than most first-generation antipsychotics.[15][16] Its use, along with the use of other typical antipsychotics, has been associated with degenerative retinopathies.[17] 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.[18] 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.[19] 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).[14] Blood dyscrasias such as agranulocytosis, leukopenia and neutropenia are possible with thioridazine treatment.[14]


Thioridazine has the following binding profile:[20]

Biologic Protein Binding affinity (Ki[nM]) Binding affinity of Mesoridazine (Ki [nM]) Binding affinity of Sulforidazine (Ki [nM]) Notes
DAT 1684 ND ND
5-HT1A 144.35 500 (HB) ND
5-HT1B 109 ND ND
5-HT1D 579 ND ND
5-HT1E 194 ND ND
5-HT2A 27.67 4.76 (HB) ND The ratio of 5-HT2A to D2 receptor binding is believed to dictate whether or not most antipsychotics are atypical or typical. In thioridazine's case its ratio of 5-HT2A to D2 receptor binding is below the level that's believed to be required for atypicality despite its relatively low extrapyramidal side effect liability in practice.[5]
5-HT2C 53 157 ND Believed to play a role in the weight gain-promoting effects of antipsychotics.[5]
5-HT3 >10000 ND ND
5-HT5A 364 ND ND
5-HT6 57.05 380 ND
5-HT7 99 73 (RC) ND
α1A 3.15 2 (HB) ND Likely the receptor responsible for the orthostatic hypotension known to occur in individuals on thioridazine.[5]
α1B 2.4 ND ND
α2A 134.15 1612.9 (HB) ND
α2B 341.65 ND ND
α2C 74.9 ND ND
β1 >10000 ND ND
β2 >10000 ND ND
M1 12.8 10 ND This receptor is believed to be the chief receptor responsible for the anticholinergic side effects of thioridazine (e.g. dry mouth, constipation, blurred vision, etc.). Likely plays a role in thioridazine's low extrapyramidal side effect liability as anticholinergic drugs such as benzatropine are routinely given to treat extrapyramidal side effects resulting from antipsychotic treatment.[5]
M2 286.33 15 ND
M3 29 90 ND
M4 310.33 19 ND
M5 12.67 60 ND
D1 94.5 ND ND
D2 0.4 4.3 0.25 Believed to be the receptor responsible for the therapeutic effects of antipsychotics.[5]
D3 1.5 2.6 0.7
D4 1.5 9.1 ND
D5 258 ND ND
hERG 191 ND ND Likely involved in thioridazine's cardiac effects.
H1 16.5 1.81 (HB) ND Likely responsible for the sedating effects of thioridazine.
H2 136 ND ND Regulates the release of hydrochloric acid into the stomach.
H4 2400 ND ND

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.


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,[21] and into (S)- and (R)-thioridazine-5-sulfoxide.[22] Mesoridazine is in turn metabolized into sulforidazine.[23] Thioridazine is an inhibitor of CYP1A2 and CYP3A2.[24]


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.

The usual dosage was 10–75 mg per day for mild cases to 600–800 mg per day for severely disturbed patients.

Thioridazine is still available from other manufacturers as a generic drug with the precaution that it is used only in psychotic patients refractory to other forms of drug treatment. ECG-monitoring and frequent white blood cell counts are required before initiating therapy and in close intervals afterwards. Low-dose thioridazine (10–50 mg per day) is somewhat popular in Russia for the treatment of somatoform disorders, panic attacks, hyperactive-impulsive type of ADHD and insomnia associated with alcohol withdrawal.

A multi-year UK study by the Alzheimer's Research Trust suggested that this and other neuroleptic anti-psychotic drugs commonly given to Alzheimer's patients with mild behavioural problems often make their condition worse.[citation needed][25] The study concluded that



Thioridazine synthesis:[27] J. Renz, J.P. Bourquin, G. Gamboni, G. Schwarb, U.S. Patent 3,239,514 (1966). Side chain synthesis:[28]


  1. ^ Shvartsburd, A; Sajadi, C; Morton, V; Mirabi, M; Gordon, J; Smith, RC (August 1984). "Blood levels of haloperidol and thioridazine during maintenance neuroleptic treatment of schizophrenic outpatients". Journal of Clinical Psychopharmacology 4 (4): 194–198. doi:10.1097/00004714-198408000-00004. PMID 6470190. 
  2. ^ a b "SHARED CARE PROTOCOL Thioridazine" (PDF). NHS Lothian Joint Formulary. March 2012. 
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  4. ^ Ichikawa J, Dai J, O'Laughlin IA, Fowler WL, Meltzer HY (March 2002). "Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine release without an effect in the nucleus accumbens or striatum". Neuropsychopharmacology 26 (3): 325–39. doi:10.1016/S0893-133X(01)00312-8. PMID 11850147. 
  5. ^ a b c d e f Brunton, L. L.; Chabner, B.; Knollmann, B. C., eds. (2011). Goodman & Gilman's The Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill. ISBN 978-0-07-162442-8. 
  6. ^ Kirchner, V; Kelly, CA; Harvey, RJ (2001). "Thioridazine for dementia". The Cochrane Database of Systematic Reviews (3): CD000464. doi:10.1002/14651858.CD000464. PMID 11686961. 
  7. ^ Amaral L, Boeree MJ, Gillespie SH, Udwadia ZF, van Soolingen D (June 2010). "Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and the need for global trials is now!". Int. J. Antimicrob. Agents 35 (6): 524–6. doi:10.1016/j.ijantimicag.2009.12.019. PMID 20188526. 
  8. ^ a b Amaral, L; Viveiros, M (May 2012). "Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections". International Journal of Antimicrobial Agents 39 (5): 376–380. doi:10.1016/j.ijantimicag.2012.01.012. PMID 22445204. 
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External links[edit]