Sulpiride

證據等級: L5

預測適應症: 9 個

Sulpiride: From Psychotic Disorder to Retinal Dystrophy with Extraocular Anomalies

One-Sentence Summary

Sulpiride is a selective dopamine D2/D3 receptor antagonist internationally used for psychotic disorders and as an antiemetic, though it currently holds no CBG-MEB marketing authorization in the Netherlands. The TxGNN model predicts it may be effective for Retinal Dystrophy with or without Extraocular Anomalies, with 0 clinical trials and 16 publications retrieved — none of which directly study this drug-disease combination.

Quick Overview

Item	Content
Original Indication	Not registered in the Netherlands; no CBG-MEB approved indication on record
Predicted New Indication	Retinal Dystrophy with or without Extraocular Anomalies
TxGNN Prediction Score	99.95%
Evidence Level	L5
NL Market Status	Not registered
Number of Authorizations	0
Recommended Decision	Hold

Why Is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available from the provided data sources. Based on known pharmacological information, Sulpiride is a benzamide-class selective antagonist at dopamine D2 and D3 receptors. It is internationally established as an atypical antipsychotic and antiemetic, though it has not been granted marketing authorization by the CBG-MEB in the Netherlands.

The theoretical mechanistic link rests on the presence of dopaminergic amacrine cells in the retina, which express D2 and D4 receptors. In some photoreceptor dystrophies, retinal dopamine signaling is known to be reduced. This provides a superficially plausible rationale for a dopaminergic intervention.

However, this link is assessed as very weak and directionally inconsistent. Sulpiride is a D2/D3 antagonist, meaning it would further suppress — not restore — retinal dopaminergic transmission. More critically, retinal dystrophies are primarily driven by photoreceptor-level genetic mutations (e.g., RPGR, CRB1), which Sulpiride has no known mechanism to correct. The TxGNN model’s high confidence score likely reflects shared graph topology rather than a biologically actionable connection.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

The 16 publications retrieved address orbital anatomy, extraocular muscle disorders, and congenital ocular anomalies in general. None directly investigate Sulpiride for retinal dystrophy. They were retrieved based on the disease category (conditions with extraocular anomalies) rather than the specific drug-disease pair, and should be interpreted accordingly.

PMID	Year	Type	Journal	Key Findings
38321238	2024	Review	Pediatric Radiology	Differential diagnosis and imaging features of pediatric ocular pathologies including congenital/developmental lesions, retinopathy of prematurity, and Coats disease
38249493	2023	Review	Taiwan Journal of Ophthalmology	Congenital anomalies of lens shape and their association with anterior segment dysgenesis and extraocular features
33806565	2021	Original article	Int J Molecular Sciences	Optic nerve head and retinal abnormalities in congenital fibrosis of extraocular muscles (CFEOM) arising from KIF21A/TUBB3 mutations
33447730	2020	Review	Therapeutic Advances in Ophthalmology	Eye involvement in inherited metabolic disorders, covering retinal, corneal, lens, and extraocular muscle abnormalities
30747268	2019	Review	Neuroradiology	Neuroradiological and clinical evaluation of ophthalmoplegia for differential diagnosis and treatment planning
30196776	2018	Review	J Binocular Vision and Ocular Motility	Congenital cranial dysinnervation disorders (CCDDs) and patterns of ophthalmoplegia; diagnostic confirmation challenges
27930425	2017	Case series	Ophthalmic Plastic & Reconstructive Surgery	The gracillimus orbitis — an anomalous accessory extraocular muscle found in 5–14% of cadaver orbits
24932988	2014	Case series	American Journal of Ophthalmology	Pathogenesis and treatment rationale for maculopathy associated with cavitary optic disc anomalies
24413161	2014	Case report	J Neuro-Ophthalmology	Isolated trochlear-oculomotor synkinesis in a 6-year-old; subset of congenital cranial dysinnervation disorders
22241537	2012	Review	Klinische Monatsblätter für Augenheilkunde	Congenital ptosis: levator muscle fatty dystrophy/fibrosis and association with refractive errors and binocular disturbances

Netherlands Market Information

Sulpiride currently holds no marketing authorization from the CBG-MEB (College ter Beoordeling van Geneesmiddelen) in the Netherlands. No RVG numbers, registered product names, or approved SmPC documents are on file. Any future use in the Netherlands would require either a full centralized EMA authorization or a national procedure through CBG-MEB.

Safety Considerations

Please refer to the SmPC (Summary of Product Characteristics) for safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: Despite a high TxGNN prediction score of 99.95%, this candidate is unsupported by any clinical trial evidence, and the retrieved literature does not study Sulpiride in the context of retinal dystrophy. Most critically, Sulpiride’s mechanism as a D2/D3 antagonist is directionally opposite to what the retinal dopamine hypothesis would require, and the underlying genetic etiology of retinal dystrophies is not addressable through dopaminergic pharmacology. The complete absence of a CBG-MEB marketing authorization creates an additional regulatory barrier.

To proceed, the following is needed:

Mechanistic validation: Preclinical studies in animal models of retinal dystrophy (e.g., rd10, RPGR-knockout mice) to determine whether D2 antagonism has any measurable neuroprotective effect on photoreceptors
MOA data gap resolution: Full mechanism of action data retrieval from DrugBank (currently unavailable — Data Gap DG002)
Genetic target analysis: Review of the specific gene mutations underlying the target disease to assess whether any pharmacological approach targeting dopamine receptors is biologically plausible
Safety data gap resolution: Download and parse the original SmPC/product information from source regulatory agencies to fill Data Gap DG001
Regulatory pathway scoping: If preclinical results are unexpectedly positive, initiate a CBG-MEB/EMA scoping discussion for a possible off-label use or compassionate use framework
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.