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European Journal of Endocrinology Jan 2019Background Dopamine agonists (DAs) are the main treatment for patients with hyperprolactinemia and prolactinomas. Recently, an increasing number of reports emphasized... (Review)
Review
Background Dopamine agonists (DAs) are the main treatment for patients with hyperprolactinemia and prolactinomas. Recently, an increasing number of reports emphasized DAs' psychological side effects, either de novo or as exacerbations of prior psychiatric disease. Methods Review of prospective and retrospective studies (PubMed 1976, September 2018) evaluating the psychological profile of DA-treated patients with hyperprolactinemia and prolactinomas. Case series and case reports of psychiatric complications were also reviewed. Results Most studies were cross-sectional and had a control group of healthy volunteers or patients with nonfunctioning pituitary adenomas. There were few prospective studies, with/without control group, that included small numbers of patients. Compared with controls, patients with hyperprolactinemia generally had worse quality of life, anxiety, depression and certain personality traits. Patients receiving DAs had higher impulsivity scores than normoprolactinemic controls. Impulse control disorders (ICDs) were reported in both genders, with hypersexuality mostly in men. Multiple ICDs were sometimes reported in the same patient, usually reversible after DA discontinuation. In case reports, DA therapy was temporally associated with severe depression, manic episodes or psychosis, which improved after discontinuation and administration of psychiatric medications. Gender type of DA, dose and duration of therapy did not correlate with occurrence of psychiatric pathology. Conclusion Patients with hyperprolactinemia receiving DAs may develop changes in mood and behavior regardless of prior psychiatric history. Increased awareness for ICDs, depression, mania and other types of psychosis is needed by all physicians who prescribe DAs. Larger prospective controlled clinical studies are needed to delineate prevalence, risk stratification and management.
Topics: Bipolar Disorder; Depression; Dopamine Agonists; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactinoma; Psychoses, Substance-Induced
PubMed: 30400048
DOI: 10.1530/EJE-18-0682 -
Australasian Psychiatry : Bulletin of... Jun 2022Cariprazine is the third partial dopamine agonist now available in Australia. This paper will review the properties, evidence and likely clinical place of cariprazine.
OBJECTIVE
Cariprazine is the third partial dopamine agonist now available in Australia. This paper will review the properties, evidence and likely clinical place of cariprazine.
CONCLUSION
Cariprazine is a partial agonist with high affinity at dopamine D and D receptors, partial agonism at 5HT receptors, moderate 5HT and H antagonism and no anticholinergic activity. It is rapidly absorbed, is unaffected by food, achieves a peak plasma level in 4-8 hours and has high bioavailability. The half-life of cariprazine and its metabolites is long (7-8 days); steady state occurs in 4-8 weeks. It is hepatically metabolized via 3A4 cytochrome enzymes. Cariprazine is an effective antipsychotic in acute schizophrenia in both short and longer placebo-controlled studies. Cariprazine appears to have small advantages in negative symptoms of schizophrenia. While not approved for bipolar disorder, cariprazine is effective in mania and mixed states but requires doses higher than current maximums recommended. Cariprazine causes more akathisia than aripiprazole or brexpiprazole but is less prone to insomnia, weight gain and sedation. Risks for hyperprolactinaemia and QT prolongation are low. Cariprazine is another 'metabolically-friendly' antipsychotic for schizophrenia, with advantages for those with negative symptoms, mood symptoms or problems with adherence.
Topics: Antipsychotic Agents; Dopamine Agonists; Humans; Piperazines; Treatment Outcome
PubMed: 35156402
DOI: 10.1177/10398562211064254 -
CNS Drugs Jul 2019Rotigotine (Neupro), a non-ergolinic dopamine agonist (DA), is administered once daily via a transdermal patch (TP) that delivers the drug over a 24-h period. In the EU,... (Review)
Review
Rotigotine (Neupro), a non-ergolinic dopamine agonist (DA), is administered once daily via a transdermal patch (TP) that delivers the drug over a 24-h period. In the EU, the rotigotine TP is approved as monotherapy for the treatment of early Parkinson's disease (PD) and as combination therapy with levodopa throughout the course of the disease. It is also approved for the treatment of PD in numerous other countries, including Australia, the USA, China and Japan. Rotigotine TP effectively improved motor and overall functioning in clinical trials in Caucasian and Asian patients with early PD (as monotherapy) or advanced PD (in combination with levodopa); treatment benefits appeared to be maintained in open-label extensions that followed patients for up to 6 years. Rotigotine TP was not consistently non-inferior to ropinirole and pramipexole in studies that included these oral non-ergolinic DAs as active comparators. Rotigotine TP variously improved some non-motor symptoms of PD, in particular sleep disturbances and health-related quality of life (HRQOL), based on findings from individual studies and/or a meta-analysis. Rotigotine TP was generally well tolerated, with an adverse event profile characterized by adverse events typical of dopaminergic stimulation and transdermal patch application. Available for more than a decade, rotigotine TP is a well-established, once-daily DA formulation for use in the short- and longer-term treatment of PD. It offers a convenient alternative when non-oral administration of medication is preferred and may be particularly useful in patients with gastrointestinal disturbances that reduce the suitability of oral medication.
Topics: Administration, Cutaneous; Dopamine Agonists; Humans; Indoles; Parkinson Disease; Pramipexole; Quality of Life; Tetrahydronaphthalenes; Thiophenes; Transdermal Patch
PubMed: 31243728
DOI: 10.1007/s40263-019-00646-y -
The Journal of Neuroscience : the... Feb 2023Impulse control and/or gambling disorders can be triggered by dopamine agonist therapies used to treat Parkinson's disease, but the cognitive and neurobiological...
Impulse control and/or gambling disorders can be triggered by dopamine agonist therapies used to treat Parkinson's disease, but the cognitive and neurobiological mechanisms underlying these adverse effects are unknown. Recent data show that adding win-paired sound and light cues to the rat gambling task (rGT) potentiates risky decision-making and impulsivity via the dopamine system, and that changing dopaminergic tone has a greater influence on behavior while subjects are learning task contingencies. Dopamine agonist therapy may therefore be potentiating risk-taking by amplifying the behavioral impact of gambling-related cues on novel behavior. Here, we show that ropinirole treatment in male rats transiently increased motor impulsivity but robustly and progressively increased choice of the high-risk/high-reward options when administered during acquisition of the cued but not uncued rGT. Early in training, ropinirole increased win-stay behavior after large unlikely wins on the cued rGT, indicative of enhanced model-free learning, which mediated the drug's effect on later risk preference. cFos imaging showed that both chronic ropinirole and the addition of win-paired cues suppressed the activity of dopaminergic midbrain neurons. The ratio of midbrain:prefrontal cFos neurons was lower in animals with suboptimal choice patterns and tended to predict risk preference across all rats. Network analyses further suggested that ropinirole induced decoupling of the dopaminergic cells of the VTA and nucleus accumbens but only when win-paired cues were present. Frontostriatal activity uninformed by the endogenous dopaminergic teaching signal therefore appeared to perpetuate risky choice, and ropinirole exaggerated this disconnect in synergy with reward-paired cues. D receptor agonists, used to treat Parkinson's disease, can cause gambling disorder through an unknown mechanism. Ropinirole increased risky decision-making in rats, but only when wins were paired with casino-inspired sounds and lights. This was mediated by increased win-stay behavior after large unlikely wins early in learning, indicating enhanced model-free learning. cFos imaging showed that ropinirole suppressed activity of midbrain dopamine neurons, an effect that was mimicked by the addition of win-paired cues. The degree of risky choice rats exhibited was uniquely predicted by the ratio of midbrain dopamine:PFC activity. Depriving the PFC of the endogenous dopaminergic teaching signal may therefore drive risky decision-making on-task, and ropinirole acts synergistically with win-paired cues to amplify this.
Topics: Rats; Male; Animals; Dopamine Agonists; Dopamine; Cues; Rats, Long-Evans; Parkinson Disease; Reward; Choice Behavior; Decision Making
PubMed: 36623876
DOI: 10.1523/JNEUROSCI.1459-22.2022 -
Australasian Psychiatry : Bulletin of... Apr 2023We sought to review the effects of Dopamine Receptor Partial Agonist (DRPA) antipsychotic medications on milk supply and breastfeeding. (Review)
Review
OBJECTIVE
We sought to review the effects of Dopamine Receptor Partial Agonist (DRPA) antipsychotic medications on milk supply and breastfeeding.
METHOD
Narrative review of selected literature including animal and human data.
RESULTS
Scant case study evidence suggests that DRPAs may lead to reduced milk supply for some.
CONCLUSIONS
Women taking DRPAs should be advised of the possibility that these may affect milk supply, and reporting should be encouraged to aid future research.
Topics: Animals; Female; Humans; Aripiprazole; Milk; Breast Feeding; Mothers; Dopamine Agonists
PubMed: 36825499
DOI: 10.1177/10398562231159510 -
JAMA Neurology Feb 2017Every year, Ramadan fasting is practiced by many Muslim individuals. In cases of chronic disease, religious texts allow fasting to be broken. However, many believers... (Review)
Review
IMPORTANCE
Every year, Ramadan fasting is practiced by many Muslim individuals. In cases of chronic disease, religious texts allow fasting to be broken. However, many believers still want to fast even at the risk of damaging their health. To our knowledge, there are no published recommendations on the medical management of Parkinson disease (PD) during Ramadan. Effective treatments exist in PD and usually require several daily drug intakes. Apart from worsening symptoms, interrupting PD treatment might lead to a severe withdrawal syndrome.
OBSERVATIONS
Although no specific studies on this topic have led to formal recommendations, we suggest some options for adapting the treatment for patients who fast during Ramadan. The general principle is based on switching the patient's treatment to an equivalent dosage of a dopamine agonist that can be administered once daily or by transdermal patch. However, such an option is only feasible for patients who require a moderate amount of PD treatment and can tolerate dopamine agonist therapy.
CONCLUSIONS AND RELEVANCE
Because many patients with PD require regular multiple daily administration of dopamine-replacement medication, the management of Ramadan fasting is not easy. Switching the patient's treatment to an equivalent dosage of a dopamine agonist that can be administered once daily or by transdermal patch seems to be a reasonable option to consider for patients treated with a low-to-moderate amount of PD medication.
Topics: Disease Management; Dopamine Agonists; Fasting; Guidelines as Topic; Humans; Islam; Parkinson Disease
PubMed: 28027343
DOI: 10.1001/jamaneurol.2016.4291 -
Nature Communications Jun 2022Dopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological...
Dopamine receptors are widely distributed in the central nervous system and are important therapeutic targets for treatment of various psychiatric and neurological diseases. Here, we report three cryo-electron microscopy structures of the D1 dopamine receptor (D1R)-Gs complex bound to two agonists, fenoldopam and tavapadon, and a positive allosteric modulator LY3154207. The structure reveals unusual binding of two fenoldopam molecules, one to the orthosteric binding pocket (OBP) and the other to the extended binding pocket (EBP). In contrast, one elongated tavapadon molecule binds to D1R, extending from OBP to EBP. Moreover, LY3154207 stabilizes the second intracellular loop of D1R in an alpha helical conformation to efficiently engage the G protein. Through a combination of biochemical, biophysical and cellular assays, we further show that the broad conformation stabilized by two fenoldopam molecules and interaction between TM5 and the agonist are important for biased signaling of D1R.
Topics: Cryoelectron Microscopy; Dopamine; Dopamine Agonists; Fenoldopam; Ligands; Receptors, Dopamine D1
PubMed: 35676276
DOI: 10.1038/s41467-022-30929-w -
Revista de Neurologia May 2021Apomorphine, 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... (Review)
Review
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.
Topics: Apomorphine; Dopamine Agonists; Humans; Parkinson Disease
PubMed: 33908619
DOI: 10.33588/rn.7209.2020658 -
Brain and Nerve = Shinkei Kenkyu No... May 2023Parkinson's disease (PD) is the second most common neurodegenerative disorder and its global incidence is on the rise. A well-established dopamine replacement therapy...
Parkinson's disease (PD) is the second most common neurodegenerative disorder and its global incidence is on the rise. A well-established dopamine replacement therapy for PD is based on dopamine deficiency, primarily due to dopaminergic neuronal loss in the substantia nigra. Current dopaminergic pharmacotherapy for PD consists of levodopa and other dopaminergic drugs, such as a dopamine agonist (DA) and monoamine oxidase B (MAOB) inhibitor, and patients with PD are administered these mainly according to age, disability of parkinsonism, and tolerance of the drugs. In the advanced stage, patients with PD usually experience motor complications, mainly the wearing-off phenomenon and dyskinesias, resulting in disabled activities of daily life. Many pharmacological options are available against motor fluctuations in patients with advanced PD, including long-acting DAs, MAOB inhibitors, and catechol-O-methyltransferase inhibitors, as adjunct alternatives for dopamine-replacement therapy. Non-dopaminergic pharmacological approaches, including zonisamide and istradefylline, which have been mainly developed in Japan, are also available. Amantadine and anticholinergic drugs may be useful in specific situations. Device-aided therapies, such as deep brain stimulation and levodopa-carbidopa intestinal gel infusion therapy, can be performed at the advanced stage. In this article, we provide an overview of recent pharmacological treatments for PD.
Topics: Humans; Parkinson Disease; Levodopa; Antiparkinson Agents; Catechol O-Methyltransferase; Dopamine Agonists
PubMed: 37194511
DOI: 10.11477/mf.1416202357 -
Expert Opinion on Pharmacotherapy Jul 2018Anxiety disorders are a common non-motor symptom of Parkinson's disease (PD) with a reported prevalence ranging from 20% to 50%. Although anxiety is associated with... (Review)
Review
INTRODUCTION
Anxiety disorders are a common non-motor symptom of Parkinson's disease (PD) with a reported prevalence ranging from 20% to 50%. Although anxiety is associated with Parkinson's disease, anxiety disorders can begin before the onset of motor symptoms, and have been linked to a possible abnormality of dopaminergic, serotonergic, and adrenergic neurons that precedes motor disturbance.
AREAS COVERED
Several studies have reported the pharmacological treatment of depression in PD, but none have been randomized clinical trials with a primary outcome measure of anxiety. Two trials showed that pharmacological intervention with tricyclic antidepressants or selective serotonin reuptake inhibitors proved beneficial in treating anxiety in PD. However, the effect size was modest. Anxiety is associated with off-periods and improved by L-Dopa, especially in patients with high levels of anxiety.
EXPERT OPINION
Decreasing off-periods is important for managing anxiety in patients with motor fluctuations. Minor suggestive data indicate that tricyclic antidepressants and selective serotonin reuptake inhibitors can be helpful with modest effect sizes, but the former can cause additional side effects. Only one study has examined the use of benzodiazepines to treat anxiety in PD, and benzodiazepines cannot be recommended because they increase the risk of falling. Further clinical studies for pharmacological intervention against anxiety are required.
Topics: Antidepressive Agents, Tricyclic; Anxiety Disorders; Dopamine; Dopamine Agonists; Humans; Nortriptyline; Parkinson Disease; Selective Serotonin Reuptake Inhibitors
PubMed: 29939821
DOI: 10.1080/14656566.2018.1485650