-
Translational Neurodegeneration Oct 2022Continuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson's disease (PD) to control motor and non-motor fluctuations ('OFF' periods).... (Review)
Review
Continuous drug delivery (CDD) is used in moderately advanced and late-stage Parkinson's disease (PD) to control motor and non-motor fluctuations ('OFF' periods). Transdermal rotigotine is indicated for early fluctuations, while subcutaneous apomorphine infusion and levodopa-carbidopa intestinal gel are utilised in advanced PD. All three strategies are considered examples of continuous dopaminergic stimulation achieved through CDD. A central premise of the CDD is to achieve stable control of the parkinsonian motor and non-motor states and avoid emergence of 'OFF' periods. However, data suggest that despite their efficacy in reducing the number and duration of 'OFF' periods, these strategies still do not prevent 'OFF' periods in the middle to late stages of PD, thus contradicting the widely held concepts of continuous drug delivery and continuous dopaminergic stimulation. Why these emergent 'OFF' periods still occur is unknown. In this review, we analyse the potential reasons for their persistence. The contribution of drug- and device-related involvement, and the problems related to site-specific drug delivery are analysed. We propose that changes in dopaminergic and non-dopaminergic mechanisms in the basal ganglia might render these persistent 'OFF' periods unresponsive to dopaminergic therapy delivered via CDD.
Topics: Antiparkinson Agents; Apomorphine; Carbidopa; Dopamine; Humans; Levodopa; Parkinson Disease
PubMed: 36229860
DOI: 10.1186/s40035-022-00317-x -
CNS Drugs Sep 2019Satisfactory management of Parkinson's disease is a challenge that requires a tailored approach for each individual. In the advanced phase of the disease, patients may... (Review)
Review
Satisfactory management of Parkinson's disease is a challenge that requires a tailored approach for each individual. In the advanced phase of the disease, patients may experience motor complications despite optimized pharmacological therapy. Apomorphine, a short-acting D- and D-like receptor agonist, is the only drug proven to have an efficacy equal to that of levodopa, albeit with a shorter time to onset and effect duration. Clinical trials have shown that intermittent apomorphine injections provide rapid and effective relief from unpredictable "off" periods. Continuous apomorphine infusion reduced around 50% of the daily "off" time in several studies. Dopaminergic side effects such as nausea, somnolence and hypotonia, as well as administration site reactions, are often mild or treatable, but somnolence and skin reactions in particular can sometimes be reasons for premature discontinuation. We provide an overview of the pharmacological mechanism of action of the drug in light of its effects on Parkinson's disease symptoms. We then summarize the evidence regarding the efficacy and tolerability of apomorphine, both in its established formulations (subcutaneous intermittent injection and continuous infusion) and in the new preparations currently under investigation.
Topics: Animals; Antiparkinson Agents; Apomorphine; Clinical Trials as Topic; Dopamine; Humans; Parkinson Disease
PubMed: 31473980
DOI: 10.1007/s40263-019-00661-z -
Journal of Neurology, Neurosurgery, and... Jul 1975Forty men, mainly alcoholics, were administered either the dopamine receptor agonist, apomorphine HCl (1 mg), or distilled water subcutaneously three times a day for 14... (Clinical Trial)
Clinical Trial
Forty men, mainly alcoholics, were administered either the dopamine receptor agonist, apomorphine HCl (1 mg), or distilled water subcutaneously three times a day for 14 days in a double blind study. None of the subjects developed an endogenous depression or schizophrenic symptoms. Scores on the Hamilton Rating Scale, Zung Self Rating Scale, and Brief Psychiatric Rating Scale showed improvement with both apomorphine and placebo. There were no significant differences between the two treatments on these rating scales. A significant incidence of spontaneous penile erections occurred after apomorphine treatment compared with placebo. Both treatments eliminated subjective craving for alcohol. Acute administration of apomorphine had no effect on psychomotor retardation or depressed mood in two patients with endogenous depression.
Topics: Alcoholism; Antidepressive Agents; Apomorphine; Bipolar Disorder; Clinical Trials as Topic; Depression; Humans; Libido; Male; Middle Aged; Penis; Placebos; Psychiatric Status Rating Scales; Psychomotor Disorders; Psychoses, Substance-Induced; Schizophrenia
PubMed: 1099172
DOI: 10.1136/jnnp.38.7.722 -
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 -
Current Pharmaceutical Design 2014Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with... (Review)
Review
Survivors of severe brain injuries may end up in a state of 'wakeful unresponsiveness' or in a minimally conscious state. Pharmacological treatments of patients with disorders of consciousness aim to improve arousal levels and recovery of consciousness. We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes of the patients' neurological status, leading sometimes to dramatic improvements. These findings are discussed in the context of current hypotheses of these agents' therapeutic mechanisms on cerebral function. In order to improve our understanding of the underlying pathophysiological mechanisms of these drugs, we suggest combining sensitive and specific behavioral tools with neuroimaging and electrophysiological measures in large randomized, double-blind, placebo-controlled experimental designs. We conclude that the pharmacokinetics and pharmacodynamics of amantadine, apomorphine and zolpidem need further exploration to determine which treatment would provide a better neurological outcome regarding the patient's etiology, diagnosis, time since injury and overall condition.
Topics: Amantadine; Apomorphine; Consciousness Disorders; Humans; Pyridines; Zolpidem
PubMed: 24025057
DOI: No ID Found -
Journal of Parkinson's Disease 2023Patients with Parkinson's disease often suffer from OFF symptoms disrupting their daily routines and adding to disabilities. Despite polypharmacy and adjustments to... (Review)
Review
Patients with Parkinson's disease often suffer from OFF symptoms disrupting their daily routines and adding to disabilities. Despite polypharmacy and adjustments to medication schedules, they often do not experience consistent relief from their motor symptoms. As the disease progresses, impaired gastric emptying may evolve, making it even more challenging for dopaminergic drugs to provide consistent results. This review focuses on a group of drugs that have the pharmacokinetic advantage of a much earlier onset of action by virtue of their non-oral routes of absorption. We compare the current marketed options: subcutaneous apomorphine, sublingual apomorphine, and inhaled levodopa. Subcutaneous apomorphine is the speediest to take effect, whereas sublingual apomorphine offers the longest clinical effect. Inhaled levodopa has the most favorable side effect profile among the three options. An inhaled form of apomorphine is currently under development, having passed safety and efficacy studies. Each of these drugs has unique characteristics for the user, including different side effect profiles and onset of action. The best choice for a patient will depend on individual needs and circumstances. In this review, we explore those nuances to allow clinicians to select the best option for their patients.
Topics: Humans; Parkinson Disease; Apomorphine; Levodopa; Antiparkinson Agents; Dopamine Agonists; Drug-Related Side Effects and Adverse Reactions
PubMed: 37182902
DOI: 10.3233/JPD-230055 -
Brazilian Journal of Medical and... Apr 2005Apomorphine is a dopamine receptor agonist proposed to be a neuroprotective agent in the treatment of patients with Parkinson's disease. Both in vivo and in vitro... (Review)
Review
Apomorphine is a dopamine receptor agonist proposed to be a neuroprotective agent in the treatment of patients with Parkinson's disease. Both in vivo and in vitro studies have shown that apomorphine displays both antioxidant and pro-oxidant actions, and might have either neuroprotective or neurotoxic effects on the central nervous system. Some of the neurotoxic effects of apomorphine are mediated by its oxidation derivatives. In the present review, we discuss recent studies from our laboratory in which the molecular, cellular and neurobehavioral effects of apomorphine and its oxidized derivative, 8-oxo-apomorphine-semiquinone (8-OASQ), were evaluated in different experimental models, i.e., in vitro genotoxicity in Salmonella/microsome assay and WP2 Mutoxitest, sensitivity assay in Saccharomyces cerevisiae, neurobehavioral procedures (inhibition avoidance task, open field behavior, and habituation) in rats, stereotyped behavior in mice, and Comet assay and oxidative stress analyses in mouse brain. Our results show that apomorphine and 8-OASQ induce differential mutagenic, neurochemical and neurobehavioral effects. 8-OASQ displays cytotoxic effects and oxidative and frameshift mutagenic activities, while apomorphine shows antimutagenic and antioxidant effects in vitro. 8-OASQ induces a significant increase of DNA damage in mouse brain tissue. Both apomorphine and 8-OASQ impair memory for aversive training in rats, although the two drugs showed a different dose-response pattern. 8-OASQ fails to induce stereotyped behaviors in mice. The implications of these findings are discussed in the light of evidence from studies by other groups. We propose that the neuroprotective and neurotoxic effects of dopamine agonists might be mediated, in part, by their oxidized metabolites.
Topics: Animals; Antiparkinson Agents; Apomorphine; Behavior, Animal; DNA Damage; Dopamine Agonists; Dose-Response Relationship, Drug; Memory; Mice; Mutagenicity Tests; Oxidation-Reduction; Quinones; Rats; Saccharomyces cerevisiae; Salmonella typhimurium
PubMed: 15962173
DOI: 10.1590/s0100-879x2005000400001 -
Journal of Neural Transmission (Vienna,... Nov 2023Dopaminergic therapies dominate the treatment of the motor and non-motor symptoms of Parkinson's disease (PD) but there have been no major advances in therapy in many... (Review)
Review
Dopaminergic therapies dominate the treatment of the motor and non-motor symptoms of Parkinson's disease (PD) but there have been no major advances in therapy in many decades. Two of the oldest drugs used appear more effective than others-levodopa and apomorphine-but the reasons for this are seldom discussed and this may be one cause for a lack of progress. This short review questions current thinking on drug action and looks at whether adopting the philosophy of ex-US Secretary of State Donald Rumsfeld reveals 'unknown' aspects of the actions of levodopa and apomorphine that provide clues for a way forward. It appears that both levodopa and apomorphine have a more complex pharmacology than classical views would suggest. In addition, there are unexpected facets to the mechanisms through which levodopa acts that are either forgotten as 'known unknowns' or ignored as 'unknown unknowns'. The conclusion reached is that we may not know as much as we think about drug action in PD and there is a case for looking beyond the obvious.
Topics: Humans; Apomorphine; Levodopa; Parkinson Disease; Antiparkinson Agents; Dopamine
PubMed: 37210460
DOI: 10.1007/s00702-023-02655-0 -
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 -
Arquivos de Neuro-psiquiatria Dec 2018Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic... (Review)
Review
Optimizing idiopathic Parkinson's disease treatment is a challenging, multifaceted and continuous process with direct impact on patients' quality of life. The basic tenet of this task entails tailored therapy, allowing for optimal motor function with the fewest adverse effects. Apomorphine, a dopamine agonist used as rescue therapy for patients with motor fluctuations, with potential positive effects on nonmotor symptoms, is the only antiparkinsonian agent whose capacity to control motor symptoms is comparable to that of levodopa. Subcutaneous administration, either as an intermittent injection or as continuous infusion, appears to be the most effective and tolerable route. This review summarizes the historical background, structure, mechanism of action, indications, contraindications and side effects, compares apomorphine infusion therapy with other treatments, such as oral therapy, deep brain stimulation and continuous enteral infusion of levodopa/carbidopa gel, and gives practical instructions on how to initiate treatment.
Topics: Antiparkinson Agents; Apomorphine; Carbidopa; Deep Brain Stimulation; Dopamine Agonists; Drug Combinations; Humans; Levodopa; Parkinson Disease
PubMed: 30698208
DOI: 10.1590/0004-282X20180140