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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 The branded product was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias.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 still available in the US.
Contents
1 Indications
2 Side effects
3 Pharmacology
4 Metabolism
5 History
6 Antibiotic activity
7 References
8 External links
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.
Side effects
For further information see: Phenothiazine
Thioridazine prolongs the QTc interval in a dose-dependent manner.
Pharmacology
Thioridazine has the following binding profile:
Biologic Protein
Binding affinity (K i [nM])
Binding affinity of Mesoridazine (K i [nM])
Binding affinity of Sulforidazine (K i [nM])
Notes
SERT
1259
ND
ND
NET
842
ND
ND
DAT
1684
ND
ND
5-HT 1A
144.35
500 (HB)
ND
5-HT 1B
109
ND
ND
5-HT 1D
579
ND
ND
5-HT 1E
194
ND
ND
5-HT 2A
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-HT 2C
53
157
ND
Believed to play a role in the weight gain-promoting effects of antipsychotics.
5-HT 3
>10000
ND
ND
5-HT 5A
364
ND
ND
5-HT 6
57.05
380
ND
5-HT 7
99
73 (RC)
ND
α 1A
3.15
2 (HB)
ND
Likely the receptor responsible for the orthostatic hypotension known to occur in individuals on thioridazine.
α 1B
2.4
ND
ND
α 2A
134.15
1612.9 (HB)
ND
α 2B
341.65
ND
ND
α 2C
74.9
ND
ND
β 1
>10000
ND
ND
β 2
>10000
ND
ND
M 1
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.
M 2
286.33
15
ND
M 3
29
90
ND
M 4
310.33
19
ND
M 5
12.67
60
ND
D 1
94.5
ND
ND
D 2
0.4
4.3
0.25
Believed to be the receptor responsible for the therapeutic effects of antipsychotics.
D 3
1.5
2.6
0.7
D 4
1.5
9.1
ND
D 5
258
ND
ND
hERG
191
ND
ND
Likely involved in thioridazine’s cardiac effects.
H 1
16.5
1.81 (HB)
ND
Likely responsible for the sedating effects of thioridazine.
H 2
136
ND
ND
Regulates the release of hydrochloric acid into the stomach.
H 4
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
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,
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
This section needs expansion. You can help by adding to it. (November 2015)
Thioridazine is known to kill XDR-TB

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