Prochlorperazine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Prochlorperazine
- Prochlorperazine: From Schizophrenia to Retinal Dystrophy (with or without Extraocular Anomalies)
Prochlorperazine: From Schizophrenia to Retinal Dystrophy (with or without Extraocular Anomalies)
One-Sentence Summary
Prochlorperazine is a phenothiazine antipsychotic, originally used for schizophrenia. The TxGNN model's top-ranked prediction is retinal dystrophy with or without extraocular anomalies, but no clinical trials and no publications currently support it. The best-supported lead among the predicted indications is manic bipolar affective disorder (7 publications, all indirect or historical, and no trials).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia (from the knowledge graph; the Singapore licence records contain no indication text) |
| Predicted New Indication | Retinal dystrophy with or without extraocular anomalies |
| TxGNN Prediction Score | 99.998% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available for this drug. Based on known information, prochlorperazine is a phenothiazine that blocks dopamine D2 receptors, and it also acts on histamine and muscarinic receptors. Its efficacy in schizophrenia and psychosis is established.
For the top-ranked prediction, retinal dystrophy, no mechanistic link has been identified. The very high score (0.99998) reflects graph-based prediction only. Retinal dystrophies are inherited disorders, and a D2 antagonist has no known disease-modifying role. The other top-ranked predictions are similar: hydranencephaly, congenital glycosylation disorders, X-linked myopia subtypes, Charcot-Marie-Tooth disease type 1G, polymicrogyria and atypical glycine encephalopathy. All are rare congenital or monogenic conditions with no plausible pharmacological rationale. These predictions are probably driven by graph topology rather than biology.
The exception is manic bipolar affective disorder (score 99.98%, rank 10). It is biologically plausible, because phenothiazine D2 antagonists are used in acute mania and agitation, and the condition is close to the original psychiatric indication. However, newer antipsychotics have much stronger evidence in mania.
Clinical Trial Evidence
Currently no related clinical trials registered, for the top-ranked prediction or for manic bipolar affective disorder.
Literature Evidence
No literature is available for the top-ranked prediction (retinal dystrophy). The following publications relate to the most plausible alternative, manic bipolar affective disorder. All are indirect or anecdotal:
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 19461391 | 2009 | Review | J Psychiatr Pract | Use and safety of antipsychotics in pregnancy; indirect relevance |
| 26819726 | 2015 | Pharmacovigilance | J Pharm Health Care Sci | Hyperglycaemic adverse events with antipsychotics in spontaneous reports (FAERS) |
| 13617778 | 1959 | Case report | Ann Med Psychol | Confusional dream-like attack caused by prochlorperazine in a mild manic-depressive patient |
| 14242542 | 1965 | Review | Obstet Gynecol | Approach to severe psychological disorders of the puerperium |
| 14233737 | 1964 | Survey/Case series | Am J Psychiatry | Electroshock therapy combined with phenothiazines and reserpine |
| 14062306 | 1963 | Review | Tunis Med | Agitation and its emergency management |
| 14222730 | 1964 | Case series | L'Encephale | Psychodysleptic manifestations during treatment with psycholeptics |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN01382P | STEMETIL INJECTION 12.5 mg/ml | Injection | Not available |
| SIN02049P | PROCHLOR TABLETS 5 mg | Tablet | Not available |
| SIN03002P | PROPERAZINE TABLET 5 mg | Tablet | Not available |
Cytotoxicity
Not applicable. Prochlorperazine is not an antineoplastic drug, so this section is omitted.
Safety Considerations
- Contraindications flagged in the knowledge graph (graph-derived associations, not package insert text):
- Cardiovascular: hypertension, orthostatic hypotension, postural orthostatic tachycardia syndrome, multiple system atrophy, long QT syndrome (including familial), torsades de pointes, coronary artery disease, myocardial infarction, coronary thrombosis.
- Neurological: epilepsy, basal ganglia disease, focal hand dystonia, blepharospasm.
- Haematological: thrombocytopenia, neutropenia, agranulocytosis.
- Organ disease: kidney disease, liver disease, gallbladder disease, pyoureter, gastric ulcer.
- Metabolic and other: hyperglycaemia, obesity disorders, benign prostatic hyperplasia, substance abuse/dependence, female breast carcinoma.
- Drug Interactions: 100 interactions were found in total; the 20 retrieved are mostly Moderate.
- Major: bupropion and potassium citrate.
- Moderate, in these groups:
- Antidiabetics (acarbose, alogliptin, metformin, pioglitazone, canagliflozin, chlorpropamide, albiglutide).
- Anticholinergics (atropine, hyoscyamine, glycopyrronium).
- Other agents (epinephrine, morphine, loperamide, clarithromycin, famotidine, lorcaserin, and the laxatives bisacodyl and picosulfuric acid).
- Package insert warnings and contraindications from the Singapore regulator could not be retrieved. Please refer to the package insert for authoritative safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction (retinal dystrophy) rests solely on a graph-based score. It has no trials, no literature and no plausible mechanism, which gives an evidence level of L5. The only credible lead, manic bipolar affective disorder (L4), is supported only by indirect or historical reports and should be treated as a research question rather than a candidate for action.
To proceed, the following is needed:
- Mechanism of action data, to allow proper mechanistic-link analysis.
- Singapore package insert warnings and contraindications (a blocking gap for safety screening).
- For manic bipolar disorder, a modern comparative evidence review against established antipsychotics.
- For the rare-disease predictions, a biological rationale before any further investment.
- Route compatibility assessment (injectable and oral forms are available in Singapore).
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.