Apomorphine

Evidence Level: L5

Predicted Indications: 10

Apomorphine

Pharmacist Assessment Report

Apomorphine: From Parkinson’s Disease to Polymicrogyria, Perisylvian, with Cerebellar Hypoplasia and Arthrogryposis

One-Sentence Summary

Apomorphine is a dopamine agonist originally used to treat Parkinson’s disease. The TxGNN model predicts it may be effective for schizophrenia, but only indirect, mostly historical literature (19 publications) and no registered clinical trials currently relate to this direction. The predicted effect runs against the usual treatment logic, so this remains a research question rather than a ready candidate.

Note: The top-ranked TxGNN prediction (polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis) has no trials or literature and no identifiable mechanistic link. This report therefore focuses on the highest-ranked prediction with literature, schizophrenia (rank 5).

Quick Overview

Item	Content
Original Indication	Parkinson’s disease (and related parkinsonian syndromes). The Australian licence entry has no indication text recorded.
Predicted New Indication	polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis
TxGNN Prediction Score	0.9969
Evidence Level	L5
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 1)
Recommended Decision	Hold (research question only)

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available in the data compiled for this report. Apomorphine is known as a direct-acting D1/D2 dopamine receptor agonist, and its efficacy in Parkinson’s disease is established. The dopamine system is also central to the dopamine hypothesis of schizophrenia, so the target system is plausibly relevant. This is likely what drives the model’s prediction.

The direction of effect is the main concern. The dopamine hypothesis implicates enhanced dopamine function in positive symptoms, and established antipsychotics block D2 receptors. A dopamine agonist would therefore be expected to worsen psychosis. A 2001 review (PMID 11394190) describes this as a “dilemma”, finding little evidence that apomorphine at doses stimulating postsynaptic receptors induces psychosis. Some older work explored low-dose effects mediated through dopamine autoreceptors, which might reduce dopamine activity.

The older studies mainly used apomorphine as a probe of dopamine receptor sensitivity, not as a therapy. Where treatment was tested, results were negative or inconclusive (see below). The prediction is therefore best viewed as a hypothesis, not a supported repurposing opportunity.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

The data compiled for this report include 19 publications. The most relevant are listed below (up to 10, prioritising clinical studies and reviews).

PMID	Year	Type	Journal	Key Findings
6372737	1984	Clinical study	Arch Gen Psychiatry	Low-dose apomorphine (0.75 mg subcutaneously) versus placebo in 25 male patients with schizophrenia; no significant improvement or deterioration in psychotic or tardive dyskinetic symptoms
6682989	1983	Clinical study (double-blind)	Prog Neuropsychopharmacol Biol Psychiatry	Low-dose apomorphine (0.01 mg/kg) in 12 chronic patients; no overall difference from placebo, though anxiety and depression subscales improved
1099172	1975	Double-blind study	J Neurol Neurosurg Psychiatry	40 men (mainly alcoholics) given apomorphine 1 mg or placebo for 14 days; no depression or schizophrenic symptoms developed
6718635	1984	Clinical study/Review (design unclear)	Psychopharmacol Bull	Apomorphine and schizophrenia (abstract not available)
6115735	1980	Not classified	Commun Psychopharmacol	Apomorphine in schizophrenia (abstract not available)
11394190	2001	Review/Commentary	J Psychiatry Neurosci	Little or no evidence that apomorphine induces psychosis or worsens symptoms at postsynaptic doses; discusses the tension with the dopamine hypothesis
540209	1979	Neuroendocrine study	Br J Psychiatry	Growth hormone and prolactin responses to apomorphine used as research probes in schizophrenia
12727131	2003	Clinical study	Psychoneuroendocrinology	Hormone responses to apomorphine in 20 untreated inpatients with schizophrenia versus controls, relating dopamine and serotonin function to symptom clusters
30805732	2019	Review	J Neural Transm	Background review of classical dopamine agonists, including parenteral apomorphine in Parkinson’s disease
33571431	2021	Structural/basic research	Cell	Cryo-EM structures of D1 and D2 receptor signalling complexes; background pharmacology only

The remaining publications are animal or model studies, or concern other agents (for example BPC 157, clozapine and aripiprazole), and do not directly support the prediction.

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 10950H	Movapo PFS	Solution for subcutaneous infusion containing apomorphine hydrochloride hemihydrate 50 mg in 10 mL pre-filled syringe	Not recorded in the data compiled for this report

Safety Considerations

Product Information warnings and contraindications were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for full safety information.

Contraindications from the knowledge graph (not label text): the TxGNN knowledge graph lists contraindication links to the following conditions. These must be verified against the PI.

Psychiatric: psychotic disorder, schizophreniform disorder, schizoaffective disorder, mental disorder, substance abuse/dependence. These are directly relevant to the proposed schizophrenia indication.
Cardiovascular: long QT syndrome (including familial), torsades de pointes, orthostatic hypotension, postural orthostatic tachycardia syndrome, coronary artery disease, cerebrovascular disorder
Neurological: multiple system atrophy, drug-induced dyskinesia
Other: liver disease, gallbladder disease, impaired renal function disease, potassium deficiency disease, priapism

Drug interactions: the interaction query returned 100 entries. The main ones in the data reviewed:

Major: alosetron, cisapride, dolasetron, granisetron (QT prolongation or related concerns are plausible; verify against the PI)
Moderate: famotidine, loperamide, bupropion, clarithromycin, levofloxacin, metoclopramide, dronabinol, and several laxatives (bisacodyl, castor oil, glycerin, lactitol, lactulose, magnesium citrate, magnesium hydroxide, mineral oil)
Minor: metronidazole

Conclusion and Next Steps

Decision: Hold

Rationale:

The schizophrenia prediction has no registered trials. The few historical treatment studies (1983–1984) found no significant benefit, and a dopamine agonist is expected to risk worsening psychosis. The knowledge graph also lists psychotic disorders as contraindications.
The other nine predictions have no trials or literature, and most have no identifiable mechanistic link.

To proceed, the following is needed:

Mechanism of action data (e.g. from DrugBank)
TGA Product Information with warnings and contraindications, and the approved indication text for the ARTG entry
A resolution of the safety question of psychosis worsening, for example through a review of the older low-dose autoreceptor hypothesis
A justification for any new route or formulation, since only a subcutaneous injectable is marketed in Australia
Only if a credible rationale emerges: a carefully designed early-phase study with close psychiatric monitoring
Disclaimer

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