Prochlorperazine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Prochlorperazine: From Schizophrenia to Retinal Dystrophy (Top TxGNN Prediction)
One-Sentence Summary
Prochlorperazine is a phenothiazine antipsychotic and antiemetic, listed in the knowledge graph as originally indicated for schizophrenia. The TxGNN model’s top-ranked prediction is retinal dystrophy with or without extraocular anomalies, but this prediction has 0 clinical trials and 0 publications behind it. The only prediction with any supporting literature is manic bipolar affective disorder (rank 10), which has 7 publications, mostly old or indirect, and no registered trials.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia (from the knowledge graph; no approved indication text is available in the US license records) |
| Predicted New Indication | Retinal dystrophy with or without extraocular anomalies |
| TxGNN Prediction Score | 99.998% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 11 (all cancelled; these are ANDA generic applications) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, prochlorperazine is a phenothiazine that acts as a dopamine D2 receptor antagonist. Its efficacy in schizophrenia and nausea is established, but nothing in the data compiled for this report connects it to inherited retinal dystrophy.
The high TxGNN score reflects a computational prediction only. No trials or literature corroborate it, and there is no supported mechanistic link between a symptomatic D2 antagonist and an inherited retinal degeneration.
The other top-ranked predictions are similarly unsupported: hydranencephaly, a congenital disorder of glycosylation, X-linked myopia, Charcot-Marie-Tooth disease type 1G, perisylvian polymicrogyria, syndromic myopia, X-linked female-limited myopia 26, and atypical glycine encephalopathy. All are rare congenital or genetic conditions with no plausible disease-modifying role for a D2 antagonist.
The one biologically plausible prediction is manic bipolar affective disorder (score 99.979%, rank 10). Its D2 antagonism is shared with antipsychotics used for acute mania and agitation. It is the closest to the original psychiatric use, but the supporting evidence is indirect (see below).
Clinical Trial Evidence
Currently no related clinical trials registered, for the top prediction or for manic bipolar affective disorder.
Literature Evidence
No literature is available for the top prediction (retinal dystrophy). The table below covers the only prediction with literature, manic bipolar affective disorder.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26819726 | 2015 | Cohort | J Pharm Health Care Sci | Analysis of hyperglycemic adverse events with antipsychotics in spontaneous adverse event reports (FAERS); a class-level safety study, not efficacy |
| 19461391 | 2009 | Review | J Psychiatr Pract | Use and safety of antipsychotic drugs during pregnancy; class-level review |
| 13617778 | 1959 | Case report | Ann Med Psychol | Confusional dream-like attack caused by prochlorperazine in a mild manic-depressive patient (an adverse reaction) |
| 14242542 | 1965 | Review | Obstet Gynecol | Approach to severe psychological disorders of the puerperium |
| 14233737 | 1964 | Review | Am J Psychiatry | Survey of electroshock therapy combined with phenothiazines and reserpine |
| 14062306 | 1963 | Review | Tunisie Med | Emergency management of agitation in general practice |
| 14222730 | 1964 | Review | L’Encephale | Psychodysleptic manifestations during treatment with psycholeptics |
None of these provides controlled efficacy data for prochlorperazine in mania.
US Market Information
All 11 US authorizations are cancelled, and none has approved indication text on record.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA216495 | Prochlorperazine Maleate (Zydus Lifesciences) | Tablet | Not available |
| ANDA040268 | Prochlorperazine Maleate (Northwind Health) | Tablet | Not available |
| ANDA040101 | Prochlorperazine Maleate (Chartwell RX) | Film-coated tablet | Not available |
| ANDA204147 | Prochlorperazine Edisylate (Avenacy) | Injection, solution | Not available |
| ANDA040246 | Compro (PD-Rx Pharmaceuticals) | Suppository | Not available |
Six further cancelled ANDAs exist (tablets, film-coated tablets and an injection) from other manufacturers.
Cytotoxicity
Not applicable. Prochlorperazine is not an antineoplastic drug, so this section is omitted.
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text):
- Cardiovascular: hypertension, orthostatic hypotension, long QT syndrome, torsades de pointes, coronary artery disease, myocardial infarction.
- Neurological: epilepsy, basal ganglia disease, focal dystonia, blepharospasm.
- Haematological: neutropenia, agranulocytosis, thrombocytopenia.
- Organ disease: liver, kidney and gallbladder disease.
- Metabolic and other: hyperglycemia, obesity, benign prostatic hyperplasia, gastric ulcer, substance abuse/dependence, female breast carcinoma.
- Drug Interactions: 100 interactions were recorded. Those listed include two Major ones: bupropion and potassium citrate. Moderate interactions include antidiabetic drugs (metformin, pioglitazone, alogliptin, acarbose, canagliflozin, chlorpropamide, albiglutide), anticholinergics (atropine, hyoscyamine, glycopyrronium), morphine, epinephrine, clarithromycin, loperamide and famotidine.
- Package-insert warnings and contraindications were not available for this report. Please refer to the package insert for the official safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction (retinal dystrophy) is supported only by a model score, with no trials, no literature and no mechanistic link (Evidence Level L5). The only plausible direction, manic bipolar affective disorder, has only indirect, largely historical evidence (Level L4), and newer antipsychotics are established alternatives. All US licenses are cancelled and the interaction burden is large.
To proceed, the following is needed:
- Package-insert warnings and contraindications (currently a blocking gap for safety screening)
- Mechanism of action data (for example from DrugBank)
- For bipolar mania: a systematic search for controlled efficacy data specific to prochlorperazine, followed by a comparison against current antipsychotics
- Clarification of the regulatory and supply situation, since no valid US license currently exists
- A mechanistic rationale and preclinical evidence before any further consideration of the retinal or other rare-disease predictions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.