Apomorphine titration with and without anti-emetic pretreatment in patients with Parkinson's disease experiencing OFF episodes: A modified Delphi panel.

Introduction: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed. Methods: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment. During Round 1, a panel of 9 US movement disorder specialists rated the appropriateness of prescribing apomorphine therapy with and without antiemetic pretreatment across 192 patient scenarios and were able to review their scores in relation to other scores. During the Round 2, consensus was defined for each scenario as either strong (>75 % agreement) or moderate (66 % agreement). Results: There was strong consensus on 118 of 192 scenario's (97 as appropriate and 21 as inappropriate), moderate consensus on 29 scenarios, some agreement on 32 scenarios, and lack of agreement on 13 scenarios. In the absence of an antiemetic, there was strong consensus that titration schedules should be flexible and based on dose response. However, the group only reached moderate consensus on the speed of titration, highlighting the need for more systematic information on this area. In the presence of an antiemetic, panelists considered usual initial dosing and flexible titration to be appropriate in most scenarios except for when the patient is already experiencing dopaminergic adverse events. Conclusions: Experts generally reached consensus that apomorphine can usually be prescribed without antiemetic pretreatment. Recommendations described here reflect the areas of greatest agreement among a panel of experts based on current available evidence.

Influence of continuous subcutaneous apomorphine infusion on cognition and behavior in Parkinson's disease: A systematic review.

INTRODUCTION: The efficacy of continuous subcutaneous apomorphine infusion (CSAI) for motor complications of Parkinson's disease (PD) is established. However, its effect on cognition and behavior remains controversial. The main objective of this systematic review was to describe the existing literature on the effects of CSAI on cognition and behavior and to determine the quality for each study. METHODS: PubMed/Medline, Embase, APA PsycInfo®, and Cochrane Library databases were searched, following PRISMA recommendations. Only longitudinal studies evaluating the effect of CSAI on cognition (global cognition, executive functions, visuospatial abilities, language, memory, attention, social cognition) and/or behavior (depression, anxiety, apathy, psychotic symptoms, impulse control disorders, neuropsychiatric fluctuations) in PD were included. The quality of the included studies was also assessed with a questionnaire. RESULTS: Twenty-three longitudinal studies evaluated the effect of CSAI on cognition and/or behavior. Overall, results were suggestive of positive effects, notably on executive functions and emotion recognition. However, there were some reports of cognitive slowing and long-term global cognitive deterioration. At the behavioral level, no study showed significant adverse effect of CSAI. Occasionally, a slight improvement of depression, anxiety, apathy, and neuropsychiatric fluctuations was reported. Nevertheless, only four studies met good quality criteria and controlled study regarding cognition were lacking. CONCLUSION: The results suggest that CSAI has no obvious negative effects on cognition and behavior in PD. This treatment even shows promise in reducing certain symptoms such as neuropsychiatric fluctuations. However, due to methodological limitations in many studies, no robust conclusions can be drawn. Further multicenter controlled trials are needed to confirm these results.

Apomorphine Suppresses the Progression of Steatohepatitis by Inhibiting Ferroptosis.

The role of ferroptosis in steatohepatitis development is largely unknown. We investigated (1) whether hepatocyte ferroptosis occurs in a gene-modified steatohepatitis model without modifying dietary components, (2) whether ferroptosis occurs at an early stage of steatohepatitis, and (3) whether apomorphine, recently reported as a ferroptosis inhibitor, can ameliorate steatohepatitis. Hepatocyte-specific PTEN KO mice were used. Huh 7 and primary cultured hepatocytes isolated from the mice were used in this study. The number of dead cells increased in 10-week-old PTEN KO mice. This cell death was suppressed by the administration of ferroptosis inhibitor ferrostatin-1 for 2 weeks. Apomorphine also ameliorated the severity of steatohepatitis. Treatment with ferroptosis inhibitors, including apomorphine, decreases the level of lipid peroxidase. Apomorphine suppressed cell death induced by RSL-3 (a ferroptosis inducer), which was not suppressed by apoptosis or necroptosis inhibitors. Apomorphine showed a radical trapping capacity with much more potent activity than ferrostatin-1 and Trolox, a soluble form of vitamin E. In addition, apomorphine activated nrf2 and its downstream genes, including HO-1 and xCT. In conclusion, ferroptosis occurs in steatohepatitis from an early stage in PTEN KO mice. In addition, apomorphine ameliorates the severity of steatohepatitis by inhibiting ferroptosis.

Memory enhancing and neuroprotective effects of apomorphine in a rat model of dementia.

Oxidative stress from generation of increased reactive oxygen species or has been reported to play an important role in dementia. Oxidative stress due to free radicals of oxygen or reactive oxygen species could be precipitating factors in the etiology of dementia. Apomorphine has been reported to have neuroprotective effects. To monitor memory enhancing and neuroprotective effects of apomorphine, we determined the antioxidant enzymes activities, lipid peroxidation, acetylcholine esterase (AChE) activity in brain and plasma, following repetitive administration of apomorphine in rat model of dementia. Biogenic amine levels were also monitored in hippocampus. Repeated administration of scopolamine was taken as an animal model of dementia. Decreased glutathione peroxidase, superoxide dismutase and catalase activities were observed in these animal models of dementia. While increased lipid peroxidation was also observed in the brain and plasma samples. The results showed significant effects of apomorphine. The activities of antioxidant enzymes displayed increased activities in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly higher in brain and plasma of apomorphine treated rats. Superoxide dismutase (SOD) was significantly decreased in plasma of scopolamine injected rats; and a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in scopolamine treated rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM). Short-term memory and long-term memory was impaired significantly in scopolamine treated rats, which was prevented by apomorphine. Moreover, a marked decrease in biogenic amines was also found in the brain of scopolamine treated rats and was reverted in apomorphine treated rats. Results showed that scopolamine-treatment induced memory impairment and induced oxidative stress in rats as compared to saline-treated controls. These impairments were significantly restored by apomorphine administration. In conclusion, our data suggests that apomorphine at the dose of 1 mg/kg could be a potential therapeutic agent to treat dementia and related disorders.

Effectiveness of Continuous Dopaminergic Therapies in Parkinson's Disease: A Review of L-DOPA Pharmacokinetics/Pharmacodynamics.

Background: Parkinson's disease (PD) is characterized by striatal dopamine deficiency. Since dopamine cannot cross the digestive and blood-brain barriers, its precursor, levodopa (L-DOPA), remains the mainstay of treatment. However, the significant pharmacokinetic (Pk) and pharmacodynamic (Pd) limitations of L-DOPA, combined with the severity of PD, may trigger motor and non-motor complications, for which continuous dopaminergic delivery therapies have been developed. Objective: The aim of this study was to review the literature on the Pk/Pd limitations of L-DOPA and how current treatments of continuous dopaminergic administration ameliorate these problems, in order to identify the need for new therapeutic avenues. Methods: A comprehensive literature search was carried out using PubMed and 75 articles were initially extracted. Following independent screening by two reviewers and consideration of eligibility, 10 articles were chosen for further analysis. Information concerning the Pk/Pd of L-DOPA was classified for each article. Results: Pk/Pd problems notably include: (i) restricted digestive and cerebral absorption; (ii) unnecessary peripheral distribution; (iii) short half-life; (iv) age- and PD-induced decline of central aromatic L-amino acid decarboxylase; (v) misdistribution in many cells; and (vii) pulsatile stimulation of dopaminergic receptors. Current treatments only slightly ameliorate some of these problems. Conclusions: Many Pk/Pd constraints are not resolved by existing continuous dopaminergic delivery therapies. This highlights the significant gap between these treatments and the ideal of continuous dopaminergic stimulation.

Sublingual apomorphine in the treatment of Parkinson's disease.

Advanced Parkinson´s disease (PD) is often complicated by fluctuations of disability depending on plasma levels of levodopa. For most patients OFF phases with worsening of tremor and immobility, but also pain, depression, autonomic symptoms are troublesome. While adjustments of levodopa administrations can relief such fluctuations for some time, "on demand" therapies become more and more important. These "on demand" therapies should provide fast and efficacious relief. During the past years, new options for on demand therapies in PD-associated OFF episodes have been developed, including new formulations of levodopa and apomorphine to provide fast and readily accessible on demand treatment. In this narrative review, the challenges of the treatment of PD-associated fluctuations and OFF states are addressed, with a special focus on sublingual apomorphine (SL-APO) including the results from recent clinical trials.

Integrating technology into a successful apomorphine delivery program in Thailand: a 10-year journey of achievements with a five-motto concept.

Introduction: Apomorphine, a potent dopamine agonist, is a therapeutic option for patients with Parkinson's disease and motor fluctuations. However, the adoption of and adherence to this therapy have been limited by the need for complex delivery devices and specialized care as well as resource consumption, posing challenges for new physicians. Thailand is a unique example of a developing nation that has successfully implemented and continued the use of this therapy by employing cooperative technology that has dramatically enhanced apomorphine delivery services. Methods: Establishing apomorphine delivery services requires significant resources and step-by-step solutions. We began our services by implementing various strategies in three chronological stages: the initial stage (2013-2015), intermediate stage (2016-2019), and current stage (2020-present), each presenting unique challenges. Together, we also implemented a proposed set of five mottos to strengthen our apomorphine delivery service. Using additive technology, we developed a patient registry platform that combined electronic data acquisition, video and remote monitoring using wearable sensors, and in-house mobile applications to support our service. Results: At the initial stage, we assembled a team to enhance the efficacy and confirm the safety of apomorphine treatment in our hospital. At the intermediate stage, we expanded our apomorphine delivery services beyond just the patients at our hospital. We supported other hospitals in Thailand in setting up their own apomorphine services by educating both physicians and nurses regarding apomorphine therapy. With this educational undertaking, increased apomorphine-related knowledge among medical professionals, and a greater number of hospitals providing apomorphine services, an increasing number of patients were administered apomorphine in subsequent years. Currently, we are providing effective apomorphine delivery to improve patient outcomes and are seamlessly integrating technology into clinical practice. Incorporating integrative technologies in our apomorphine delivery program yielded positive results in data collection and support throughout patient care, in tracking patients' statuses, in the long-term use of this treatment, and in increasing medication adherence rates. Conclusion: This perspective paper describes how technology can help provide supportive healthcare services in resource-constrained environments, such as in Thailand, offering a step-by-step approach to overcoming several limitations. The valuable insights from our 10-year journey in successfully integrating technology into apomorphine delivery services can benefit new physicians seeking to replicate our success.

Model-based comparison of subcutaneous versus sublingual apomorphine administration in the treatment of motor fluctuations in Parkinson's disease.

The objective of this study was to compare the effectiveness of subcutaneous (SC) and sublingual (SL) formulations of apomorphine for the treatment of motor fluctuations in Parkinson's disease using a pharmacokinetics (PK)/pharmacodynamics (PD) modeling approach. The PK of SC and SL apomorphine are best described by a one-compartment model with first-order absorption and a two-compartment model with delayed absorption, respectively. The PK/PD model relating apomorphine plasma concentrations to the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores was described by a sigmoidal Emax model assuming effective concentration = drug concentration in an effect compartment. Apomorphine concentrations and UPDRS motor scores were simulated from the PK/PD models using 500 hypothetical subjects. UPDRS motor score change from baseline was evaluated using time to clinically relevant response, response duration, area under the curve, maximal response, and time to maximal response. Higher doses of each apomorphine formulation were associated with shorter time to response, longer response duration, and greater maximal response. Although the mean maximal responses to SC and SL apomorphine were comparable, the time to response was four times shorter (7 vs. 31 min) and time to maximal response was two times shorter (27 vs. 61 min) for 4 mg SC vs. 50 mg SL. Thus, faster onset of action was observed for the SC formulation compared to SL. These data may be useful for physicians when selecting "on demand" therapy for patients with Parkinson's disease experiencing motor fluctuations.

Use of abdominal thrusts is associated with improved rates of successful emesis induction in dogs.

OBJECTIVE: To evaluate the effect of abdominal thrusts as a synergistic procedure to IV apomorphine administration on the occurrence and rate of onset of successful induction of emesis in dogs. ANIMALS: 31 client-owned dogs. METHODS: Dogs in which induction of emesis via IV apomorphine was prescribed by the attending clinician were prospectively randomized to either receive abdominal thrusts performed by a nurse or clinician or to have no physical interventions performed following IV apomorphine administration. Data collected included signalment, weight, reason for emesis, time from suspected ingestion to presentation, time from the dog's last meal to presentation, dose of apomorphine administered in milligrams, and time from apomorphine administration to emesis. RESULTS: Emesis induction was successful in 14 of 14 (100%) of the dogs in the abdominal thrust group and 13 of 17 (76.5%) in the control group (P = .02). In dogs with successful emesis, median time to emesis was 90.5 seconds (range, 36 to 348 seconds) in the abdominal thrust group and 106 seconds (range, 37 to 360 seconds) in the control group (P = .29). CLINICAL RELEVANCE: Abdominal thrusts were associated with an increased frequency of successful emesis in dogs following IV apomorphine, but did not shorten the rate of onset of emesis in dogs that vomited. Application of abdominal thrusts may be beneficial in dogs in which emesis is indicated and that do not have a clear contraindication.

[The homecare provider, a little-known player in the care of Parkinson's patients]. / Le prestataire de santé à domicile, un acteur méconnu dans la prise en charge du patient parkinsonien.

Setting up a device-based treatment for a Parkinson's patient at home is a complex affair. The homecare nurse, an expert in this pathology, coordinates the various professionals working with the patient, and is the privileged contact for the prescribing doctor. Thanks to his or her wide range of skills, he or she can provide invaluable assistance to ensure that the patient's care goes smoothly.

Intranasal and intravenous apomorphine outperform ropinirole ocular drops for induction of emesis in dogs within ten minutes: a randomized, controlled clinical trial.

OBJECTIVE: The primary goal was to compare the efficacy of administration of apomorphine (APO) administered by intranasal (IN), transconjunctival (TC), SC and IV routes with ropinirole eye drops for induction of emesis in dogs with a secondary goal to evaluate the time of emesis as well as difficulty in administration. ANIMALS: 125 client-owned dogs. METHODS: Dogs were randomly enrolled between October 1, 2021, and March 30, 2022, into groups of 25: IV APO, IN APO, TC APO, SC APO, and ropinirole eye drops. The IV, SC, and TC groups were dosed at 0.03 mg/kg, the IN group was dosed at 0.06 mg/kg, and the ropinirole group was dosed according to manufacturer guidelines. Data collected included success rate of emesis within 600 seconds, time to emesis, time to administer, and difficulty score. Results were compared to IV with P values and CIs being adjusted for multiple comparisons. RESULTS: Emesis was successful within 600 seconds using IV APO in 22 of 25 dogs. By comparison, IN APO induced emesis in 18 of 25 dogs (P = .63). Ropinirole (14/25), SC APO (6/25), and TC APO (4/25) were significantly less successful (P = .047, P = < .001, and P < 0.001, respectively). When emesis was successful, it occurred most rapidly with TC APO, followed by IN APO and then ropinirole. It was most difficult to administer IV APO and TC APO. CLINICAL RELEVANCE: Similar to IV APO, IN APO was a rapid, easy, and effective method of inducing emesis in dogs and should be considered when IV administration is not possible. Ropinirole was easy to administer but successfully induced emesis less reliably within a 10-minute timeframe. APO administered TC using the commercially compounded injectable formulation was ineffective.

Long-term safety, tolerability and efficacy of apomorphine sublingual film in patients with Parkinson's disease complicated by OFF episodes: a phase 3, open-label study.

BACKGROUND: Apomorphine sublingual film (SL-APO) is an on-demand treatment for OFF episodes in patients with Parkinson's disease (PD). OBJECTIVE: To assess the long-term (≥ 3 years) safety/tolerability and efficacy of SL-APO. METHODS: Study CTH-301 ( http://www. CLINICALTRIALS: gov NCT02542696; registered 2015-09-03) was a phase 3, multicentre, open-label study of SL-APO in PD patients with motor fluctuations, comprised of a dose-titration and long-term safety phase. All participants received SL-APO. The primary endpoint was safety/tolerability (treatment-emergent adverse events [TEAEs]) during the long-term safety phase. Efficacy assessments included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (motor examination), assessed at weeks 24, 36 and 48 during the first year of the long-term safety phase. RESULTS: 496 patients were included and 120 (24.2%) completed the long-term safety phase. Mean duration of SL-APO exposure was 294.3 days. TEAEs related to study drug were experienced by 65.3% of patients (most common: nausea [6.0%], stomatitis [1.8%], lip swelling [1.8%], dizziness [1.6%], oral mucosal erythema [1.6%], mouth ulceration [1.6%]). TEAEs leading to study drug withdrawal were experienced by 34.0% of patients (most common: nausea [5.4%], lip swelling [4.5%], mouth ulceration [2.6%], stomatitis [2.3%]). A clinically meaningful reduction in MDS-UPDRS part III score was observed as soon as 15 min following administration of SL-APO, with peak effects observed approximately 30 min post-dose and sustained up to 90 min post-dose; results were consistent over 48 weeks. CONCLUSIONS: SL-APO was generally well tolerated and efficacious over the long term as an on-demand treatment for OFF episodes in patients with PD.

Neuropharmacological assessment and identification of possible lead compound (apomorphine) from Hygrophila spinosa through in-vivo and in-silico approaches.

The aim of this research is to examine possible neurological activity of methanol, ethyl acetate, and aqueous extracts of Hygrophila spinosa and identify possible lead compounds through in silico analysis. In vivo, neuropharmacological activity was evaluated by using four distinct neuropharmacological assessment assays. Previously reported GC-MS data and earlier literature were utilized to identify the phytochemicals present in Hygrophila spinosa. Computational studies notably molecular docking and molecular dynamic simulations were conducted with responsible receptors to assess the stability of the best interacting compound. Pharmacokinetics properties like absorption, distribution, metabolism, excretion, and toxicity were considered to evaluate the drug likeliness properties of the identified compounds. All the in vivo results support the notion that different extracts (methanol, ethyl acetate, and aqueous) of Hygrophila spinosa have significant (*p = 0.05) sedative-hypnotic, anxiolytic, and anti-depressant activity. Among all the extracts, specifically methanol extracts of Hygrophila spinosa (MHS 400 mg/kg.b.w.) showed better sedative, anxiolytic and antidepressant activity than aqueous and ethyl acetate extracts. In silico molecular docking analysis revealed that among 53 compounds 7 compounds showed good binding affinities and one compound, namely apomorphine (CID: 6005), surprisingly showed promising binding affinity to all the receptors . An analysis of molecular dynamics simulations confirmed that apomorphine (CID: 6005) had a high level of stability at the protein binding site. Evidence suggests that Hygrophila spinosa has significant sedative, anxiolytic, and antidepressant activity. In silico analysis revealed that a particular compound (apomorphine) is responsible for this action. Further research is required in order to establish apomorphine as a drug for anxiety, depression, and sleep disorders.Communicated by Ramaswamy H. Sarma.

Terminal Care in Parkinson's Disease: Real-Life Use of Continuous Subcutaneous Apomorphine Infusion to Improve Patient Comfort.

BACKGROUND: There are currently no recommendations on the therapeutic management of Parkinson's disease (PD) patients at the end of life. OBJECTIVE: To describe a cohort of patients with PD who benefited from continuous subcutaneous apomorphine infusion (CSAI) initiation at the end of their life as comfort care. METHODS: This real-life cohort includes 14 PD patients, who benefited from 24-h, low-dose CSAI (0.5-3 mg/h) in the context of terminal care. Patient's comfort (pain, rigidity, and/or ability to communicate) and occurrence of CSAI-related side-effects (nausea/vomiting, cutaneous and behavioral manifestations) were evaluated based on medical records. RESULTS: All patients (age 62-94 years, disease duration 2-32 years) presented with late-stage PD and a compromised oral route. Treatment lasted from a few hours to 39 days. CSAI led to substantial functional improvement, with a good safety profile. Overall clinical comfort was deemed improved by the medical team, the patient, and/or caregivers. CONCLUSIONS: CSAI might be a promising approach in PD terminal care, as it reduces motor symptoms and overall discomfort, with an apparent good safety profile. Use of the apomorphine pen, sublingual film or a classic syringe pump might be considered when apomorphine pumps are not available. Larger observational cohorts and randomized controlled trials are needed to establish the efficacy and tolerability of apomorphine in the context of terminal care and more broadly, in an advance care planning perspective.

Potentiometric detection of apomorphine in human plasma using a 3D printed sensor.

Apomorphine is a dopamine agonist that is used for the management of Parkinson's disease and has been proven to effectively decrease the off-time duration, where the symptoms recur, in Parkinson's disease patients. This paper describes the design and fabrication of the first potentiometric sensor for the determination of apomorphine in bulk and human plasma samples. The fabrication protocol involves stereolithographic 3D printing, which is a unique tool for the rapid fabrication of low-cost sensors. The solid-contact apomorphine ion-selective electrode combines a carbon-mesh/thermoplastic composite as the ion-to-electron transducer and a 3D printed ion-selective membrane, doped with the ionophore calix[6]arene. The sensor selectively measures apomorphine in the presence of other biologically present cations - sodium, potassium, magnesium, and calcium - as well as the commonly prescribed Parkinson's pharmaceutical, levodopa (L-Dopa). The sensor demonstrated a linear, Nernstian response, with a slope of 58.8 mV/decade over the range of 5.0 mM-9.8 µM, which covers the biologically (and pharmaceutically) relevant ranges, with a limit of detection of 2.51 µM. Moreover, the apomorphine sensor exhibited good stability (minimal drift of just 188 µV/hour over 10 h) and a shelf-life of almost 4 weeks. Experiments performed in the presence of albumin, the main plasma protein to which apomorphine binds, demonstrate that the sensor responds selectively to free-apomorphine (i.e., not bound or complexed forms). The utility of the sensor was confirmed through the successful determination of apomorphine in spiked human plasma samples.

Apomorfina y disfunción frontal en la enfermedad de Parkinson / Apomorphine and frontal dysfunction in Parkinson’s disease

Introducción: El trastorno disejecutivo y la apatía son síntomas característicos de la disfunción frontal ligada a la enfermedad de Parkinson. El efecto de la infusión continua subcutánea de apomorfina en la disfunción frontal no se conoce con detalle. Desarrollo: Se ha realizado una búsqueda y análisis de los trabajos publicados más relevantes en este campo. La apomorfina logra mejorías en las pruebas que miden tareas como la planificación, la atención, la fluencia verbal y la apatía. Conclusiones: Debido a su perfil farmacológico distintivo, con mayor actividad sobre los receptores dopaminérgicos de tipo D1, la apomorfina puede resultar beneficiosa en la disfunción frontal de la enfermedad.(AU)

Introduction: Dysexecutive disorder and apathy are characteristic symptoms of frontal dysfunction linked to Parkinson’s disease. The effect of continuous subcutaneous apomorphine infusion is not known in detail. Development: A search for the most relevant studies published to date in this field was carried out, along with their analysis. Apomorphine achieves improvements in tests that measure tasks such as planning, attention, verbal fluency and apathy. Conclusions: Due to its distinctive pharmacological profile, with enhanced activity on D1-type dopaminergic receptors, apomorphine may have beneficial effects on the frontal dysfunction produced by the diseas.(AU)

The prevalence of impulsive compulsive behaviors in patients treated with apomorphine infusion: a retrospective analysis / Prevalência de comportamentos impulsivo-compulsivos em pacientes tratados com infusão de apomorfina: análise retrospectiva

ABSTRACT Background: Impulsive compulsive behaviors (ICBs) can affect a significant number of Parkinson's disease (PD) patients. Objective: We have studied brain samples from a brain bank of PD patients who received apomorphine via continuous infusion in life to assess the prevalence and outcome of ICBs. Methods: A search on the Queen Square Brain Bank (QSBB) database for cases donated from 2005 to 2016 with a pathological diagnosis of idiopathic PD was conducted. Notes of all donors who used apomorphine via continuous infusion for at least three months were reviewed. Clinical and demographic data were collected, as well as detailed information on treatment, prevalence and outcomes of ICBs. Results: 193 PD cases, 124 males and 69 females, with an average age at disease onset of 60.2 years and average disease duration of 17.2 years were reviewed. Dementia occurred in nearly half of the sample, depression in one quarter, and dyskinesias in a little over 40%. The prevalence of ICBs was 14.5%. Twenty-four individuals used apomorphine infusion for more than three months. Patients on apomorphine had younger age at disease onset, longer disease duration, and higher prevalence of dyskinesias. The prevalence of de novo ICB cases among patients on apomorphine was 8.3%. Apomorphine infusion was used for an average of 63.1 months on an average maximum dose of 79.5 mg per day. Ten patients remained on apomorphine until death. Conclusions: Apomorphine can be used as an alternative treatment for patients with previous ICBs as it has low risk of triggering recurrence of ICBs.

RESUMO Antecedentes: Comportamentos impulsivo-compulsivos (CICs) podem acometer uma parcela significativa de indivíduos com doença de Parkinson (DP). Objetivo: Nós estudamos amostras de tecido cerebral de uma população de pacientes com DP de um banco de cérebros que receberam apomorfina por infusão contínua em vida, com a finalidade de avaliar a prevalência e o desfecho dos CICs. Métodos: Uma pesquisa no banco de dados do Banco de Cérebros de Queen Square foi conduzida à procura de doações recebidas entre 2005 e 2016 com diagnóstico anatomopatológico de DP idiopática. Os prontuários de todos os doadores que usaram apomorfina por infusão contínua por um período mínimo de três meses foram revisados. Dados clínicos e demográficos foram coletados, assim como informações detalhadas sobre o tratamento, prevalência e desfecho dos CICs. Resultados: 193 casos de DP, 124 do sexo masculino e 69 do sexo feminino, com idade média de início da doença de 60,2 anos e tempo médio de duração da doença de 17,2 anos, foram revisados. Aproximadamente metade dos casos apresentaram demência, um quarto depressão, e um pouco mais de 40% discinesias. A prevalência de CICs foi 14,5%. Vinte e quatro indivíduos usaram infusão de apomorfina por mais de três meses. Os pacientes que usaram apomorfina apresentaram DP mais cedo, maior duração da doença, e uma maior prevalência de discinesias. A prevalência de novos casos de CICs entre pacientes usando apomorfina foi de 8,3%. Infusão de apomorfina foi usada em média por 63,1 meses a um dose máxima média de 79,5 mg por dia. Dez pacientes permaneceram usando apomorfina até o óbito. Conclusões: Apomorfina pode ser usada como opção de tratamento alternativo para pacientes que apresentarem CICs no passado considerando seu baixo risco de causar recorrência de CICs.

Apomorfina: un poderoso aliado en la enfermedad de Parkinson / Apomorphine: a powerful ally in Parkinson’s disease

Introducción: La apomorfina, agonista dopaminérgico D1 y D2, es el fármaco más antiguo con efectividad en el tratamiento de la enfermedad de Parkinson (EP) y el único de potencia análoga a la levodopa. Su utilidad, tanto en la administración intermitente como en la perfusión continua en el control de las fluctuaciones motoras, está demostrada tanto en estudios abiertos como controlados. Objetivo: Analizar el papel de la apomorfina en las distintas manifestaciones y momentos evolutivos de la EP mediante una revisión narrativa de la literatura científica (1951-2020). Desarrollo: Más allá del aumento de la duración del on, la reducción del off, la mejoría de la distonía en off y la calidad de vida en pacientes con EP avanzada, existe evidencia de la efectividad de la apomorfina en áreas menos conocidas de la EP, como síntomas no motores, menor riesgo de inducir trastornos de control de impulsos, potencial para atenuar las alucinaciones visuales, mejora de la clínica neuropsiquiátrica asociada a la EP, ayuda a un mejor control de las discinesias o influencia en los síntomas axiales. Sin embargo, el momento óptimo de su instauración sigue siendo objeto de debate, y existen varios factores que históricamente han limitado el uso de este valioso fármaco. Conclusiones: La apomorfina es un fármaco con propiedades únicas dentro del abanico de posibilidades para tratar la EP, con potenciales aplicaciones más allá del control de las fluctuaciones motoras. Conocerlas para indicarlas a los pacientes que más puedan beneficiarse de ellos, así como valorar adecuadamente el estadio de la EP en que iniciar la apomorfina, puede ser clave para mejorar el control clínico de esta compleja patología.(AU)

Introduction: Apomorphine, a D1-D2 dopamine agonist, is the oldest drug with proven efficacy in the treatment of Parkinson’s disease (PD), and the only with similar symptomatic power to levodopa. Its usefulness in the control of motor fluctuations, both as intermittent injections and in continuous subcutaneous infusion, has been demonstrated in open label and placebo controlled trials. Aim: To analyse the role of apomorphine in the varied clinical symptoms and different clinical stages of PD through a narrative review of scientific literature (1951-2020). Development: Beyond on-time increase, off-time decrease, off dystonia and quality of life improvement in advanced PD, there is evidence to support a role of apomorphine in less known clinical areas of PD, such as non motor symptoms, a lower risk of impulse control disorders, potential to ameliorate visual hallucinations, improve neuropsychiatric symptoms and dyskinesia and even axial features. Nevertheless, the optimal timing of apomorphine treatment remains controversial, and its implementation of this valuable drug in clinical practice has been historically hindered by several factors. Conclusions: Apomorphine is a unique drug in the PD treatment scenario, with a number of potential applications beyond motor fluctuations control. Acknowledging these properties, selecting the patient most likely to benefit from it and finding the right timing may be key in the symptomatic control of this complex disease.(AU)

Effect of dopamine and its receptors on the development of visual deprivation myopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#Myopic population of China is already nearly 600 million, the rate of teenager myopic occupies the first place in the world, myopia hsa already became one of the main diseases that endangers our adolescent's health. Dopamine is the main catecholamine in retina. Many studies have found that increasing the content of dopamine can effectively inhibit the development of myopia. Form-deprivation myopia is a classical method of myopia modeling. By observing the influence of dopamine and its receptors on the development of form-deprivation myopia, its role in the development of myopia can be reflected, and it is of great significance to guide and control the occurrence and development of myopia. In this paper, the effects of dopamine and its receptors on the development of form-deprivation myopia were reviewed in order to provide reference for the prevention and treatment of myopia.