Tiotixene

Overview

Tiotixene, or thiothixene, is a typical antipsychotic sold under the brand name Navane which is predominantly utilised to treat schizophrenia. Beyond its primary indication, it can exhibit a variety of effects common to neuroleptic drugs including anxiolytic, anti-depressive, and anti-aggressive properties.[1][2] WP

The drug was first synthesized and marketed in 1967 under the pharmaceutical company Pfizer. While the usage of the drug has declined in recent decades, the drug continues to be manufactured and prescribed in the US and Canada.[1][3][4][5] WP

Being a member of the thioxanthene class, it is chemically related to other typical neuroleptic agents such as chlorprothixene, clopenthixol, flupenthixol, and zuclopenthixol. Tiotixene also shares structural similarities with thioproperazine and pipotiazine, which are members of the phenothiazine class. WP

Drug class

Typical antipsychotic WP

From the Wikipedia article's infobox.

Uses, dosage and effects

Medical uses

Tiotixene is a widely used drug for the treatment of various psychiatric disorders such as schizophrenia, bipolar disorder, mania, and behavioural disturbances. The drug regulates behaviour and thoughts, and can also exhibit an anti-depressive effect.[2][6][7] WP

The side effect profile is similar to related antipsychotic agents, displaying weight gain, mental distress, and inability to sit still. Other possible symptoms include anticholinergic side effects such as insomnia, blurred vision, and dry mouth. Less frequently encountered side effects are drug-induced movement disorders such as Parkinsonism and tardive dyskinesia.[8–11] WP

The results of various dose-response studies (10–60 mg) indicate a stimulating effect at lower doses, which diminishes as higher doses are administered. Overall, the efficacy of thiothixene when compared to other antipsychotic drugs was evaluated to be at least as effective regardless of the optimum dosage.[12][13][14] WP

Pharmacology

Pharmacokinetics

As common with tricyclic psychotherapeutic agents, tiotixene is rapidly and extensively absorbed. Peak serum concentration of the drug is achieved after 1–3 hours. After absorption, the compound and its metabolites are spread widely throughout the body.[15][16] WP

The drug's metabolism proceeds rapidly and primarily in the liver. Although N-demethyltiotixene was identified as its major metabolite, the metabolic mechanisms remain elusive. After metabolism, most of the material is excreted through the faeces.[1][15][17] WP

Pharmacodynamics

Tiotixene shares its mechanism with related thioxanthenes which are all fundamentally used to control schizophrenia. Their mechanism of action involves the inhibition of different receptors, including 5-HT (serotonin), dopaminergic, histaminergic, and adrenergic receptors. Blocking these receptors results in a reduction of synaptic levels of dopamine, serotonin, and other neurotransmitters that are involved with abnormal excitement in the brain during psychoses. This reduction of abnormal neurotransmission activity tends to alleviate the psychotic indications associated with schizophrenia.[18][19][20] WP

Tiotixene acts primarily as a highly potent antagonist of the dopamine D₂ and D₃ receptors (subnanomolar affinity). It is also an antagonist of the histamine H₁, α₁-adrenergic, and serotonin 5-HT₇ receptors (low nanomolar affinity), as well as of various other receptors to a much lesser extent (lower affinity). It does not have any anticholinergic activity. Antagonism of the D₂ receptor is thought to be responsible for the antipsychotic effects of tiotixene.[21] WP

Efferocytosis

Thiothixene stimulates macrophages to clear pathogenic cells by inducing arginase 1 and continual efferocytosis.[22] WP

Toxicology

Thiothixene has demonstrated toxicity in animal studies and isolated human tissue, displaying cytotoxic effects against various cell types. Observed toxic effects included growth inhibition of mouse fibroblasts, inhibition of protein synthesis by human glioma cells, and inhibition of leukocyte DNA synthesis.[23][24] WP

Other compounds within the thioxanthene class have demonstrated hepatotoxicity in rodent experiments, and although anecdotal reports of thiothixene-induced liver failure exist, scientific data regarding the correlation lacks. The absence of observational or longitudinal human studies on thiothixene in published literature precludes drawing conclusions regarding the significance of toxic effects at therapeutic dosages.[25] WP

Toxicity

Chemistry

Formula

C23H29N3O2S2 PC

CAS number

3313-26-6 PC

Molar mass (g/mol)

443.6 PC

IUPAC name (computed by PubChem)

(9Z)-N,N-dimethyl-9-[3-(4-methylpiperazin-1-yl)propylidene]thioxanthene-2-sulfonamide PC

SMILES

CN1CCN(CC1)CC/C=C\2/C3=CC=CC=C3SC4=C2C=C(C=C4)S(=O)(=O)N(C)C PC

InChIKey

GFBKORZTTCHDGY-UWVJOHFNSA-N PC

PubChem CID

941651

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

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22. Journal / agency The antipsychotic drug thiothixene stimulates macrophages to clear pathogenic cells by inducing arginase 1 and continual efferocytosis | Science Signaling. 2025-04-09. doi:10.1126/scisignal.ads6584
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