Eye drop psychosis in Parkinson's disease: a cautionary tale

Ferris, Amy; Mohamed, Biju; Thomas, Chris

doi:10.1002/pnp.515

Cited by 4 publications

(11 citation statements)

References 8 publications

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“…Synthesized from 19c (0.090 g, 0.176 mmol) and acetone (3.5 mL, 0.05 M) using the general procedure for the synthesis of C6/C7 aziridines to afford 20c (0.085 g, >99%) as a brown solid that was used without further purification. 1 (1R,2R,4S,5S)-9-Methyl-3-phenyl-3,9-diazatricyclo[3.3.1.0 2,4 ]nonane (21a). Synthesized from 20a (0.059 g, 0.171 mmol, 1.0 equiv), hydrazine monohydrate (0.025 mL, 0.256 mmol, 1.5 equiv), Raney Ni (0.020 g, 0.342 mmol, 2.0 equiv), 37% CH 2 O (aq) (0.014 mL, 0.188 mmol, 1.1 equiv), and MeOH (1.7 mL, 0.1 M) following the general procedure for the deprotection-reduction-reductive amination sequence.…”

Section: Tert-butyl 5-((1r2s4r5s)-9-(13-dioxoisoindolin-2-yl)-39diaza...mentioning

confidence: 99%

“…The product was purified by chromatography on silica gel using EtOAc/MeOH/NH 4 OH (9:1:0.1) to afford 21c (0.045 g, 71%) as a tan solid. 1 H NMR (400 MHz, CDCl 3 ): δ 7.96 (d, J = 7.5 Hz, 1H), 7.54 (d, J = 3.8 Hz, 1H), 7.12 (d, J = 2.3 Hz, 1H), 7.02 (dd, J = 8.8, 2.3 Hz, 1H), 6.45 (d, J = 3.8 Hz, 1H), 3.31 (s, 2H), 2.81 (s, 2H), 2.60 (s, 3H), 2.00−1.89 (m, 2H), 1.87−1.77 (m, 1H), 1.66 (s, 9H), 1.51−1.41 (m, 1H), 1.32 (dd, J = 13.2, 6.6 Hz, 2H) ppm; 13 tert-Butyl 4-((1R,2R,4S,5S)-9-Methyl-3,9-diazatricyclo[3.3.1.0 2,4 ]nonan-3-yl)-1H-indole-1-carboxylate (21d). Synthesized from 20d (0.100 g, 0.206 mmol, 1.0 equiv), hydrazine monohydrate (0.030 mL, 0.310 mmol, 1.5 equiv), Raney Ni (0.024 g, 0.412 mmol, 2.0 equiv), 37% CH 2 O (aq) (0.017 mL, 0.227 mmol, 1.1 equiv), and MeOH (2.0 mL, 0.1 M) following the general procedure for the deprotectionreduction-reductive amination sequence.…”

Section: Tert-butyl 5-((1r2s4r5s)-9-(13-dioxoisoindolin-2-yl)-39diaza...mentioning

confidence: 99%

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Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity

Warren,

Chow,

Chytil

et al. 2024

J. Med. Chem.

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Tropane-containing small molecules like scopolamine are a promising class of psychoplastogens. However, their potent antagonism of all muscarinic receptor subtypes presents the potential for undesirable anticholinergic side effects. In an effort to decouple their neuroplasticity-promoting effects from their muscarinic activity, we performed phenotypic structure−activity relationship studies across a variety of structurally distinct subclasses of tropanes. We discovered several novel tropanes capable of significantly increasing cortical neuronal growth while exhibiting drastically reduced activity at all muscarinic receptor subtypes compared to scopolamine.

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Section: Tert-butyl 5-((1r2s4r5s)-9-(13-dioxoisoindolin-2-yl)-39diaza...mentioning

confidence: 99%

Section: Tert-butyl 5-((1r2s4r5s)-9-(13-dioxoisoindolin-2-yl)-39diaza...mentioning

confidence: 99%

Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity

Warren,

Chow,

Chytil

et al. 2024

J. Med. Chem.

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“…Even though psychiatric side effects are rare with topical forms, still psychosis and delirium have been reported with them. [ 51 , 52 ] Central anticholinergic syndrome has also been described,[ 53 ] the manifestations of which include psychotic symptoms.…”

Section: Ophthalmic Drugs Causing Psychiatric Side Effectsmentioning

confidence: 99%

Psychiatric aspects of ophthalmic disorders

Mamtani

Chaturvedi

2023

Indian Journal of Ophthalmology

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Ophthalmic disorders have psychiatric aspects associated with them at various levels. Psychological factors have a well-documented role in the causation, aggravation, and maintenance of various ophthalmic conditions, including glaucoma, central serous retinopathy, dry eye disease, and retinitis pigmentosa. Many ophthalmic conditions, including blindness, have psychological manifestations as well, which need to be addressed, in addition to the ophthalmic pathology. There is also significant overlap in the treatment of the two disciplines in many ways. For instance, many ophthalmic drugs have psychiatric side effects. Even ophthalmological surgeries have psychiatric aspects associated with them, which primarily include black patch psychosis and anxiety in the operation theater. This review will be useful for psychiatrists and ophthalmologists, for their clinical practice and research. Future research should focus on this interface to give it its well-deserved attention.

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“…Physicians and caregivers should monitor patients treated with anticholinergic drugs for associated adverse side effects 95 (Box 3), which include urinary retention, blurred vision, hallucinations and confusion. 96 Patients with PD who have cognitive impairments are more susceptible to developing these side effects, 3 or increased Alzheimer's disease pathology.…”

Section: Pharmacological Therapies To Reduce or Prevent Sialorrhoeamentioning

confidence: 99%

“…Adverse events associated with anticholinergic drug treatment. 95 A patient with PD, reported that sialorrhoea was the symptom of their disease causing the majority of their concern, because they were unable to sit down to read the newspaper without experiencing severe sialorrhoea. After no response to nonpharmacological methods of management, off-label oral administration of atropine eye drops (10 mg/ml 0.5 ml per day) was trialled.…”

Section: Pharmacological Therapies To Reduce or Prevent Sialorrhoeamentioning

confidence: 99%

The burden of sialorrhoea in chronic neurological conditions: current treatment options and the role of incobotulinumtoxinA (Xeomin®)

Morgante

Bavikatte

Anwar

et al. 2019

Ther Adv Neurol Disord

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Sialorrhoea is a frequent symptom of neurological diseases (e.g. Parkinson’s disease, motor neuron disease, cerebral palsy, and stroke) and is defined as excessive saliva accumulation leading to unintentional loss of saliva from the mouth. Sialorrhoea increases the overall burden on the patient and their caregivers, the impact of which can be both physical and psychosocial. Treatments for sialorrhoea range from lifestyle and behavioural guidance, to medications, surgery or radiation. Nonpharmacological interventions include advice on posture, swallowing control, cough management, dietary changes, eating and drinking techniques, and behavioural modification; however, these conservative measures may be ineffective for people with progressive neurological conditions. The pharmacological treatment of sialorrhoea is challenging because medications licensed for this purpose are limited, but treatments can include anticholinergic drugs and botulinum toxins. Surgical treatment of sialorrhoea is typically reserved as a last resort for patients. IncobotulinumtoxinA (Xeomin®) is the first botulinum toxin type A to receive US and UK marketing authorization for the symptomatic treatment of chronic sialorrhoea due to neurological disorders in adults. In this review, we discuss and compare the frequency and method of administration, location of treatment delivery, approximate annual costs and main side effects of botulinum toxin and different anticholinergic drugs. Management of patients with chronic neurological conditions requires input from multiple specialist teams and thus a multidisciplinary team (MDT) approach is considered fundamental to ensure that care is consistent and tailored to patients’ needs. To ensure that adult patients with neurological conditions receive the best care and sialorrhoea is well managed, we suggest a potential clinical care pathway for sialorrhoea with a MDT approach, which healthcare professionals could aspire to.

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Eye drop psychosis in Parkinson's disease: a cautionary tale

Cited by 4 publications

References 8 publications

Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity

Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity

Psychiatric aspects of ophthalmic disorders

The burden of sialorrhoea in chronic neurological conditions: current treatment options and the role of incobotulinumtoxinA (Xeomin®)

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