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|Trade names||Truxal, others|
|AHFS/Drugs.com||Micromedex Detailed Consumer Information|
|Oral, intramuscular injection|
|Biological half-life||8–12 hours|
|Chemical and physical data|
|Molar mass||315.861 g/mol|
|3D model (JSmol)|
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 yet. Likewise, it is unclear, if chlorprothixene has genuine (intrinsic) analgesic effects. However, chlorprothixene can be used as comedication in severe chronic pain. Also, like most antipsychotics, chlorprothixene has antiemetic 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%).
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.
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.
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 .
|Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.|
- 5-HT2: antipsychotic effects, anxiolysis, weight gain
- D1, D2, D3: 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, tachycardia
Because of its potent serotonin 5-HT2A 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.
One metabolite of chlorprothixene is N-desmethylchlorprothixene.
Chlorprothixene (2-chloro-9[(1-dimethylamino)-3-propyliden]thioxanthene) is made starting from 2-chlorothioxanthone. 2-Chlorothioxantone, in turn, is prepared from 2-mercaptobenzoic acid (1), the reaction of which with 1-bromo-4-chlorobenzene (2) forms 2-(4-chlorophenylthio)benzoic acid 5, which upon reaction with phosphorus pentachloride transforms into acid chloride (6), and further undergoes intramolecular cyclization with the use of aluminum chloride to give 2-chlorthioxantone (6).
An alternative way of making 2-chlorthioxantone (7) is by making 2-(4-chlorophenylthio)benzoic acid (5) by reacting 2-iodobenzoic acid (3) with 4-chlorothiophenol (4).
The resulting 2-chlorothioxantone is reacted as a carbonyl component with either 3-dimethylaminopropylmagnesiumbromide (see Engelhardt above), or with allylmagnesiumbromide, giving the corresponding tertiary alcohols 8, and 9.
Dehydration of the tertiary (8) is accomplished by acylation of the tertiary hydroxyl group using acetyl chloride and the subsequent pyrolysis of the formed acetate, which leads to the desired chlorprothixene. In the second case, dehydration of the tertiary alcohol (9) is accomplished by chlorination of the tertiary alcohol group by thionyl chloride, forming the diene 2-chloro-9-(3-propen-1-iliden)thioxanthene (10), the addition to which of dimethylamine at high temperature forms the desired chlorprothixene (11).
Society and culture
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.
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