Английская Википедия:Chlorprothixene

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Chlorprothixene, sold under the brand name Truxal among others, is a typical antipsychotic of the thioxanthene group.

Medical uses

Chlorprothixene's principal indications are the treatment of psychotic disorders (e.g. schizophrenia) and of acute mania occurring as part of bipolar disorders.

Other uses are pre- and postoperative states with anxiety and insomnia, severe nausea / emesis (in hospitalized patients), the amelioration of anxiety and agitation due to use of selective serotonin reuptake inhibitors for depression and, off-label, the amelioration of alcohol and opioid withdrawal. It may also be used cautiously to treat nonpsychotic irritability, aggression, and insomnia in pediatric patients.

An intrinsic antidepressant effect of chlorprothixene has been discussed, but not proven. Likewise, it is unclear if chlorprothixene has genuine (intrinsic) analgesic effects. However, chlorprothixene can be used as co-medication in severe chronic pain. Also, like most antipsychotics, chlorprothixene has antiemetic effects.

Side effects

Chlorprothixene has a strong sedative activity with a high incidence of anticholinergic side effects. The types of side effects encountered (dry mouth, massive hypotension and tachycardia, hyperhidrosis, substantial weight gain etc.) normally do not allow a full effective dose for the remission of psychotic disorders to be given. So cotreatment with another, more potent, antipsychotic agent is needed.

Chlorprothixene is structurally related to chlorpromazine, with which it shares, in principle, all side effects. Allergic side effects and liver damage seem to appear with an appreciable lower frequency. The elderly are particularly sensitive to anticholinergic side effects of chlorprothixene (precipitation of narrow angle glaucoma, severe obstipation, difficulties in urinating, confusional and delirant states). In patients >60 years the doses should be particularly low.

Early and late extrapyramidal side effects may occur but have been noted with a low frequency (one study with a great number of participants has delivered a total number of only 1%).Шаблон:Citation needed

Overdose

Overdose symptoms can be confusion, hypotension, and tachycardia, and several fatalities have been reported with concentrations in postmortem blood ranging from 0.1 to 7.0 mg/L compared to non-toxic levels in postmortem blood which can extend to 0.4 mg/kg.

Interactions

Chlorprothixene may increase the plasma-level of concomitantly given lithium. In order to avoid lithium intoxication, lithium plasma levels should be monitored closely.

If chlorprothixene is given concomitantly with opioids, the opioid dose should be reduced (by approx. 50%), because chlorprothixene amplifies the therapeutic actions and side effects of opioids considerably.

Avoid the concomitant use of chlorprothixene and tramadol (Ultram). Seizures may be encountered with this combination.

Consider additive sedative effects and confusional states to emerge, if chlorprothixene is given with benzodiazepines or barbiturates. Choose particular low doses of these drugs.

Exert particular caution in combining chlorprothixene with other anticholinergic drugs (tricyclic antidepressants and antiparkinsonian agents): Particularly the elderly may develop delirium, high fever, severe obstipation, even ileus and glaucoma .

Pharmacology

Pharmacodynamics

Chlorprothixene

Site	Ki (nM)	Species	Ref
Шаблон:Abbrlink	110	Шаблон:Abbr
Шаблон:Abbrlink	21–532	Human
Шаблон:Abbrlink	1,699	Шаблон:Abbr
5-HT1A	138–230	Human
5-HT2A	0.30–0.43	Human
5-HT2B	Шаблон:Abbr	Шаблон:Abbr	Шаблон:Abbr
5-HT2C	4.5	Шаблон:Abbr
5-HT3	398	Шаблон:Abbr
5-HT6	3.0–3.2	Rat
5-HT7	5.0–5.6	Rat
α1	1.0	Шаблон:Abbr
α2	186	Шаблон:Abbr
β	>10,000	Mammal
D1	12–18	Human
D2	3.0–5.6	Human
D3	1.9–4.6	Human
D4	0.65	Human
D5	9.0	Human
H1	0.89–3.8	Human
H3	>1,000	Human
Шаблон:Abbrlink	41	Шаблон:Abbr
M1	11–26	Human
M2	28–79	Human
M3	22	Human
M4	18	Human
M5	25	Human
σ	603	Шаблон:Abbr
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Chlorprothixene is an antagonist of the following receptors:

• 5-HT₂, 5-HT₆, 5-HT₇: antipsychotic effects, sedation/anxiolysis, antidepressant effect, weight gain
• D₁, D₂, D₃, D₄, D₅: antipsychotic effects, sedation, extrapyramidal side effects, prolactin increase, depression, apathy/anhedonia, weight gain
• H₁: sedation, weight gain
• Muscarinic acetylcholine receptors: anticholinergic effects, inhibition of extrapyramidal side effects
• α₁-Adrenergic: hypotension, sedation, anxiolysis

Because of its potent serotonin 5-HT_2A and muscarinic acetylcholine receptor antagonism, chlorprothixene causes relatively mild extrapyramidal symptoms. This is in contrast to most other typical antipsychotics. For this reason, chlorprothixene has sometimes been described instead as an atypical antipsychotic.

Chlorprothixene has also been found to act as FIASMA (functional inhibitor of acid sphingomyelinase).

Pharmacokinetics

One metabolite of chlorprothixene is N-desmethylchlorprothixene.Шаблон:Citation needed

Файл:Desmethylchlorprothixene.svg

Structure of N-desmethylchlorprothixene

History

Chlorprothixene was the first of the thioxanthene antipsychotics to be synthesized. It was introduced in 1959 by Lundbeck.

Lometraline, tametraline, and sertraline were reportedly derived via structural modification of chlorprothixene.Шаблон:Citation needed

Society and culture

Brand names

Chlorprothixene is sold mainly under the brand name Truxal.

Availability

Chlorprothixene is widely available throughout Europe and elsewhere in the world. The drug was previously available in the United States under the brand name Taractan, but this formulation has since been discontinued and the drug is no longer available in this country.