出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/06/08 05:24:32」(JST)
| Clinical data | |
|---|---|
| AHFS/Drugs.com | Consumer Drug Information |
| MedlinePlus | a682119 |
| License data |
|
| Pregnancy category |
|
| Routes of administration |
Oral |
| ATC code |
|
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | incomplete |
| Metabolism | hepatic (at least partly mediated by CYP2D6) |
| Biological half-life | 21-24 hours[2] |
| Excretion | faeces |
| Identifiers | |
|
IUPAC name
|
|
| CAS Number |
|
| PubChem CID |
|
| IUPHAR/BPS |
|
| DrugBank |
|
| ChemSpider |
|
| UNII |
|
| KEGG |
|
| ChEBI |
|
| ChEMBL |
|
| ECHA InfoCard | 100.000.041 |
| Chemical and physical data | |
| Formula | C21H26N2S2 |
| Molar mass | 370.577 |
| 3D model (Jmol) |
|
|
SMILES
|
|
|
InChI
|
|
| (verify) | |
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 The branded product was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias.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.[1]
Thioridazine was voluntarily discontinued by its manufacturer, Novartis, worldwide because it caused severe cardiac arrhythmias.[1][3][4][5]
Its primary use in medicine was the treatment of schizophrenia.[6] It was also tried with some success as a treatment for various psychiatric symptoms seen in people with dementia,[7] but chronic use of thioridazine and other anti-psychotics in people with dementia is not recommended.[8]
For further information see: Phenothiazine
Thioridazine prolongs the QTc interval in a dose-dependent manner.[9] It produces significantly less extrapyramidal side effects than most first-generation antipsychotics.[10][11] Its use, along with the use of other typical antipsychotics, has been associated with degenerative retinopathies.[12] 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.[13] 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.[14] 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).[9] Blood dyscrasias such as agranulocytosis, leukopenia and neutropenia are possible with thioridazine treatment.[9]
Thioridazine has the following binding profile:[15]
| Biologic Protein | Binding affinity (Ki[nM]) | Binding affinity of Mesoridazine (Ki [nM]) | Binding affinity of Sulforidazine (Ki [nM]) | Notes |
|---|---|---|---|---|
| SERT | 1259 | ND | ND | |
| NET | 842 | ND | ND | |
| 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.[6] |
| 5-HT2C | 53 | 157 | ND | Believed to play a role in the weight gain-promoting effects of antipsychotics.[6] |
| 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.[6] |
| 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.[6] |
| 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.[6] |
| 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,[16] and into (S)- and (R)-thioridazine-5-sulfoxide.[17] Mesoridazine is in turn metabolized into sulforidazine.[18] Thioridazine is an inhibitor of CYP1A2 and CYP3A2.[19]
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.[1][3]
| This section needs expansion. You can help by adding to it. (November 2015) |
Thioridazine is known to kill XDR-TB[20][21] and to make MRSA sensitive to β-lactam antibiotics.[22][23] A possible mechanism of action for the drug's antibiotic activity is via the inhibition of bacterial efflux pumps.[21]
Antipsychotics (neuroleptics) (N05A)
|
|
|---|---|
| Typical |
|
| Atypical |
|
| Others |
|
|
|
Adrenergic receptor modulators
|
|||||
|---|---|---|---|---|---|
| α1 |
|
||||
| α2 |
|
||||
| β |
|
||||
|
|||||
Acetylcholine receptor modulators
|
|||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
|
|||||||||||
|
|||||||||||
|
|||||||||||
|
|||||||||||
|
|||||||||||
|
See also: Receptor/signaling modulators
|
|||||||||||
Dopamine receptor modulators
|
|||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D1-like |
|
||||||||||||||||||||||||||||
| D2-like |
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
Histamine receptor modulators
|
|
|---|---|
| H1 |
|
| H2 |
|
| H3 |
|
| H4 |
|
|
See also: Receptor/signaling modulators • Monoamine metabolism modulators • Monoamine reuptake and release modulators
|
|
Tricyclics
|
|
|---|---|
| Classes |
|
| Antidepressants (TCAs and TeCAs) |
|
| Antihistamines |
|
| Antipsychotics |
|
| Anticonvulsants |
|
| Others |
|
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
| リンク元 | 「チオリダジン」 |
| 関連記事 | 「hydrochloride」 |