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Expert Opinion on Emerging Drugs Dec 2023In Parkinson's disease, dopamine depletion in the basal ganglia leads to symptoms including bradykinesia, gait abnormalities, and cognitive impairment. Even with... (Review)
Review
INTRODUCTION
In Parkinson's disease, dopamine depletion in the basal ganglia leads to symptoms including bradykinesia, gait abnormalities, and cognitive impairment. Even with treatment, the disease course leads to decreases in the amount of dopamine produced and released into the synapse. As dopamine production falls and the treatment course is insufficient to match the metabolic supply and demand, acute 'off' periods develop that cause reemergence of symptoms. Apomorphine is used to reverse these 'off' periods and restore function in patients with Parkinson's. This review will provide clinicians a concise article to read to learn more about apomorphine and its appropriate utilization.
AREAS COVERED
The research discussed is focused on the history, pharmacokinetics, and mechanism of action of Apomorphine. Its utilization as a treatment for Parkinson's Disease and its comparison to currently utilized drugs is also discussed in this review. We focused on articles published on PubMed and Google Scholar within the last 10 years, but in some instances had to go as far back as 1951 to include early articles published about apomorphine.
EXPERT OPINION
The expert opinion section focuses on the ways in which apomorphine could be administered in the future to better promote utilization and increase tolerability.
Topics: Humans; Apomorphine; Parkinson Disease; Dopamine; Dopamine Agonists; Injections, Subcutaneous; Antiparkinson Agents
PubMed: 37909462
DOI: 10.1080/14728214.2023.2278677 -
Revista de Neurologia Jun 2022Dysexecutive disorder and apathy are characteristic symptoms of frontal dysfunction linked to Parkinson's disease. The effect of continuous subcutaneous apomorphine... (Review)
Review
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 disease.
Topics: Apomorphine; Humans; Infusions, Subcutaneous; Parkinson Disease
PubMed: 35635363
DOI: 10.33588/rn.7411.2022080 -
Drugs in R&D 2004Bertek Pharmaceuticals, a subsidiary of Mylan Laboratories Inc., is developing an intermittent subcutaneous formulation of apomorphine hydrochloride as a treatment for... (Review)
Review
Bertek Pharmaceuticals, a subsidiary of Mylan Laboratories Inc., is developing an intermittent subcutaneous formulation of apomorphine hydrochloride as a treatment for Parkinson's disease. Apomorphine injection (APO-go) for the treatment of Parkinson's disease was launched in the UK in May 2002. Bertek licensed the formulation from Britannia Pharmaceuticals in the UK for development and marketing in the US. In April 2004, apomorphine injection was approved as the first and only therapy in the US for the acute, intermittent treatment of hypomobility, 'off' episodes associated with advanced Parkinson's disease. This approval follows the fast-track status designation given by the US FDA in January 2003, and an approvable letter issued in July 2003. The product is expected to be available by July 2004.
Topics: Antiparkinson Agents; Apomorphine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Injections, Subcutaneous; Parkinson Disease
PubMed: 15230626
DOI: 10.2165/00126839-200405040-00004 -
Parkinsonism & Related Disorders Dec 2016Apomorphine is often considered an archetypal dopamine agonist used in the treatment of Parkinson's disease (PD). However, it can be clearly differentiated from most... (Review)
Review
Apomorphine is often considered an archetypal dopamine agonist used in the treatment of Parkinson's disease (PD). However, it can be clearly differentiated from most other commonly used dopamine agonists on the basis of its pharmacology and on its unique clinical profile. Like levodopa and dopamine, apomorphine acts as a potent, direct and broad spectrum dopamine agonist activating all dopamine receptor subtypes. It also has affinity for serotonin receptors, and α-adrenergic receptors. Apomorphine is usually titrated to a dose that provides an equivalent antiparkinsonian response to that provided by levodopa, and its subcutaneous delivery allows a rapid onset of action, usually within 7-10 min. The mode of apomorphine delivery impacts on its clinical profile so as to provide two very different approaches to therapy in PD. When administered as an acute subcutaneous injection, it induces reliable and rapid relief from OFF periods underscoring its utility as a rescue medication. When given as a subcutaneous infusion, it significantly improves overall daily OFF time and there is also evidence to suggest that, in those patients who replace most or all of their oral drugs with apomorphine infusion, dyskinesia may also improve. In this paper, we review the rich pharmacology of apomorphine and review its efficacy in PD based on data from clinical trials.
Topics: Animals; Antiparkinson Agents; Apomorphine; Clinical Trials as Topic; Humans; Parkinson Disease
PubMed: 27979722
DOI: 10.1016/j.parkreldis.2016.12.003 -
Molecular Pharmaceutics 2006Apomorphine is a potent molecule for the treatment of Parkinson's disease (PD). It can be obtained in both the R and S forms, and it is the former that is the... (Review)
Review
Apomorphine is a potent molecule for the treatment of Parkinson's disease (PD). It can be obtained in both the R and S forms, and it is the former that is the therapeutically active form. Due to its structural similarity with 3,4-dihydroxyphenethylamine, dopamine, apomorphine can function as an agonist in the treatment of PD as it can stimulate both the D1 and D2 receptors of the striatum. The clinical efficacy of apomorphine is similar to that of 3,4-dihydroxyphenylalanine, levodopa (L-dopa), the cornerstone drug in dopaminergic therapy. (R)-Apomorphine is efficacious for one of the most challenging aspects in the management of PD, namely, managing the unpredictable "on-off" period as a rescue medication after oral administration of a therapeutic drug such as L-dopa. The effectiveness is due to its rapid control of the wearing-off period of the orally administered medicine. This short review will trace the progress of apomorphine use starting with its initial discovery and the first indications for which it was used, discovery of its "cure" for PD, and the studies that led to demonstrating its therapeutic efficacy. The key structural features of apomorphine responsible for its activity are illustrated along with major issues of chemical stability. From a drug delivery point of view, the current form of administration of apomorphine and some of the potential alternate methods of delivery are reviewed.
Topics: Antiparkinson Agents; Apomorphine; Dopamine Agonists; Drug Stability; History, 20th Century; Humans; Parkinson Disease; Structure-Activity Relationship
PubMed: 16889431
DOI: 10.1021/mp060012c -
Drugs in R&D Jun 2018Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with... (Review)
Review
Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson's disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its synthesis, pharmacological development, and numerous indications in human and veterinary medicine, in light of its most recent uses and newest challenges. From shamanic rituals in ancient Egypt and Mesoamerica, to the treatment of erectile dysfunction, from being discarded as a pharmacological tool to becoming an essential antiparkinsonian drug, the path of apomorphine in the therapeutic armamentarium has been tortuous and punctuated by setbacks and groundbreaking discoveries. Throughout history, three main clinical indications stood out: emetic (gastric emptying, respiratory disorders, aversive conditioning), sedative (mental disorders, clinical anesthesia, alcoholism), and antiparkinsonian (fluctuations). New indications may arise in the future, both in PD (palliative care, nonmotor symptoms, withdrawal of oral dopaminergic medication), and outside PD, with promising work in neuroprotection or addiction.
Topics: Animals; Antiparkinson Agents; Apomorphine; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Humans
PubMed: 29546602
DOI: 10.1007/s40268-018-0230-3 -
Expert Review of Neurotherapeutics 2015Apomorphine (APO) is a potent D1 and D2 dopamine agonist. Plasma maximal concentration is reached in 8-16 min with a plasma half-life of 34-70 min. Bioavailability is... (Review)
Review
Apomorphine (APO) is a potent D1 and D2 dopamine agonist. Plasma maximal concentration is reached in 8-16 min with a plasma half-life of 34-70 min. Bioavailability is close to 100%. It has a rapid antiparkinsonian action after subcutaneous (s.c.) administration with a size effect comparable with that of levodopa. Trials of s.c., oral, sublingual, intravenous, rectal, intranasal and iontophoretic transdermal administration of APO have been attempted in Parkinson's disease (PD), each of these routes have shown some potential for clinical effectiveness but the majority of studies indicate that APO intermittent s.c. administration, on which this review is mainly focused, is an effective therapy for the management of motor symptoms in PD, particularly in advanced phases mainly characterized by motor fluctuations, such as wearing OFF and unpredictable "off". Data on the effect of APO on non-motor symptoms in PD patients are limited but there is strong suggestion of a beneficial effect that warrants further investigation.
Topics: Antiparkinson Agents; Apomorphine; Clinical Trials as Topic; Humans; Parkinson Disease; Treatment Outcome
PubMed: 26037961
DOI: 10.1586/14737175.2015.1051468 -
The International Journal of... May 2024A majority of advanced Parkinson's disease (PD) patients on oral levodopa experience motor fluctuations, including sudden OFF and delayed ON periods. Fast-acting rescue... (Review)
Review
A majority of advanced Parkinson's disease (PD) patients on oral levodopa experience motor fluctuations, including sudden OFF and delayed ON periods. Fast-acting rescue medications are a vital part of the clinician's armamentarium in the treatment of motor fluctuations. Sublingual apomorphine is the first sublingual rescue medication on the market for the treatment of OFF times in PD. Here, we review the development and pharmacology of apomorphine in the treatment of PD as well as the safety and efficacy of sublingual apomorphine established in clinical trials. Finally, we compare sublingual apomorphine to the other rescue medications available and provide our opinion on the use of sublingual apomorphine in clinical practice. Clinical trials have demonstrated that sublingual apomorphine is a safe and effective option in the treatment of motor fluctuations in PD. In a Phase II trial, 100% of patients who achieved a full ON response did so within 30 min and 40% did so within 15 min. The mean duration of effect was 50 min. In a Phase III trial, 77.3% of patients achieved a full ON response. Side effects such as nausea, dizziness and somnolence were common but were generally mild. No patients experienced worsening dyskinesia. Sublingual apomorphine will provide patients with motor fluctuations due to advanced PD another safe and effective option for the treatment of OFF times.
Topics: Humans; Apomorphine; Parkinson Disease; Administration, Sublingual; Antiparkinson Agents
PubMed: 35986574
DOI: 10.1080/00207454.2022.2115908 -
CNS Drugs Feb 2015Current research shows that apomorphine is an effective treatment for symptoms of Parkinson's Disease (PD). The highly lipophilic structure allows apomorphine to cross... (Review)
Review
Current research shows that apomorphine is an effective treatment for symptoms of Parkinson's Disease (PD). The highly lipophilic structure allows apomorphine to cross cell membranes rapidly, leading to the rapid onset of action for on/off symptoms of PD. The use of apomorphine was limited in the past due to peripheral side effects, but with the advent of better delivery systems and medications to control side effects, apomorphine is better tolerated and more widely in use. The major delivery systems are continuous subcutaneous infusions and intermittent subcutaneous injections, but other delivery routes are under investigation. The purpose of this article is to discuss the current use of apomorphine, the current delivery systems and to discuss future research.
Topics: Antiparkinson Agents; Apomorphine; Drug Delivery Systems; Humans; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 25676564
DOI: 10.1007/s40263-014-0221-z -
Expert Opinion on Drug Metabolism &... Nov 2012Erectile dysfunction (ED) is a common condition affecting men. Apomorphine is one of the oral medications that has been used in the management of ED, though over recent... (Review)
Review
INTRODUCTION
Erectile dysfunction (ED) is a common condition affecting men. Apomorphine is one of the oral medications that has been used in the management of ED, though over recent years, its use in the management of ED has dwindled.
AREAS COVERED
The authors review the evidence available for the use of apomorphine in the management of ED. A Medline search was performed searching for the articles related to the use of apomorphine in the treatment of ED from 2000 to present. The article reviews the erectogenic properties of apomorphine and evaluates its efficacy, suitability and tolerability in management of patients with ED.
EXPERT OPINION
Apomorphine SL is more effective than placebos in treating ED and is generally well tolerated in the sublingual formulation, causing tolerable side effects. Newer nasal-spray formulations provide faster efficacy. Its efficacy in patients with multiple co-morbidities is more limited. However, it is not as effective as PDE5-I in the treatment of ED. Its most significant strength is its safety profile. It may have a niche in the treatment ED in patients who have failed treatment with, or are intolerant to other well-established pharmacological treatment for ED (e.g., PDE5-Is). Apomorphine is not a first-line treatment option for patients with ED, especially as it is no more widely available in the western world.
Topics: Administration, Sublingual; Animals; Apomorphine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation; Drug Evaluation, Preclinical; Erectile Dysfunction; Humans; Male; Randomized Controlled Trials as Topic; Treatment Failure; United States
PubMed: 22998347
DOI: 10.1517/17425255.2012.727797