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The Journal of Pharmacology and... Apr 2018Although dystonia is often associated with abnormal dopamine neurotransmission, dopaminergic drugs are not currently used to treat dystonia because there is a general...
Although dystonia is often associated with abnormal dopamine neurotransmission, dopaminergic drugs are not currently used to treat dystonia because there is a general view that dopaminergic drugs are ineffective. However, there is little conclusive evidence to support or refute this assumption. Therefore, to assess the therapeutic potential of these compounds, we analyzed results from multiple trials of dopamine receptor agonists in patients with idiopathic dystonias and also tested the efficacy of dopamine receptor agonists in a mouse model of generalized dystonia. Our results suggest that dopamine receptor agonists were effective in some, but not all, patients tested. Further, the mixed D1/D2 dopamine receptor agonist apomorphine was apparently more effective than subtype selective D2 dopamine receptor agonists. However, rigorously controlled trials are still needed. In a mouse model of dystonia, a selective D1 dopamine receptor agonist was not effective while a selective D2 dopamine receptor had modest efficacy. However, when combined, these receptor-selective agonists acted synergistically to ameliorate the dystonia. Coactivation of D1 and D2 dopamine receptors using apomorphine or by increasing extracellular concentrations of dopamine was also effective. Thus, results from both clinical trials and tests in mice suggest that coactivation of D1 and D2 dopamine receptors may be an effective therapeutic strategy in some patients. These results support a reconsideration of dopamine receptors as targets for the treatment of dystonia, particularly because recent genetic and diagnostic advances may facilitate the identification of the subtypes of dystonia patients who respond and those who do not.
Topics: Animals; Biogenic Monoamines; Dopamine Agonists; Dystonia; Female; Humans; Male; Mice; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 29348266
DOI: 10.1124/jpet.117.246348 -
ACS Chemical Neuroscience Mar 2020Kinetic analysis of dopamine receptor activation and inactivation and the study of dopamine-dependent signaling requires precise simulation of the presynaptic release of...
Kinetic analysis of dopamine receptor activation and inactivation and the study of dopamine-dependent signaling requires precise simulation of the presynaptic release of the neurotransmitter dopamine and tight temporal control over the release of dopamine receptor antagonists. The 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group was conjugated to dopamine and the dopamine receptor antagonist sulpiride to generate "caged" versions of these neuromodulators (CyHQ--DA and CyHQ-sulpiride, respectively) that could release their payloads with 365 or 405 nm light or through 2-photon excitation (2PE) at 740 nm. These compounds are stable under physiological conditions in the dark, yet photolyze rapidly and cleanly to yield dopamine or sulpiride and the caging remnant CyHQ-OH. CyHQ--DA mediated the light activation of dopamine-1 (D1) receptors on the breast cancer cell line MDA-MB-231 in culture. In mouse brain slice from the substantia nigra pars compacta, localized flash photolysis of CyHQ--DA accurately mimicked the natural presynaptic release of dopamine and activation of dopamine-2 (D2) receptors, causing a robust, concentration-dependent, and repeatable G protein-coupled inwardly rectifying potassium channel-mediated outward current in whole-cell voltage clamp recordings that was amplified by cocaine and blocked by sulpiride. Photolysis of CyHQ-sulpiride rapidly blocked synaptic activity, enabling measurement of the unbinding rates of dopamine and quinpirole, a D2 receptor agonist. These tools will enable more detailed study of dopamine receptors, their interactions with other GPCRs, and the physiology of dopamine signaling in the brain.
Topics: Animals; Dopamine; Dopamine Agonists; Dopaminergic Neurons; Kinetics; Mice; Quinpirole; Receptors, Dopamine D1; Sulpiride
PubMed: 32077679
DOI: 10.1021/acschemneuro.9b00675 -
Environmental Science and Pollution... Jul 2022Diabetes is a global health concern that has affected almost 415 million people globally. Bromocriptine is a dopamine D2 agonist, which is a Food and Drug Administration... (Review)
Review
Diabetes is a global health concern that has affected almost 415 million people globally. Bromocriptine is a dopamine D2 agonist, which is a Food and Drug Administration (FDA)-approved drug to treat type 2 diabetes mellitus (T2DM) patients. However, it is considered that a novel treatment therapy is required which can be used in the treatment of diabetes with or without other antidiabetic agents. Dopamine agonists are usually used in neurological disorders like Parkinson's disease (PD), restless leg syndrome, and hyperprolactinemia. However, dopamine agonists including bromocriptine and cabergoline are also effective in reducing the glycemic level in T2DM patients. Bromocriptine was formerly used for the treatment of PD, hyperprolactinemia, and restless leg syndrome, but now it is used for improving glycemic levels as well as reducing free fatty acids and triglycerides. In addition, cabergoline has been found to be effective in glycemic control, but this drug is yet to be approved by the FDA due to its limitations and lack of study. Findings of the clinical trials of bromocriptine have suggested that it reduces almost 0.4-0.8% glycated hemoglobin and cardiovascular risk by 40% in insulin-resistant patients. Moreover, the safe use of bromocriptine in obese T2DM patients makes it a more attractive option as it causes weight loss. Indeed, bromocriptine is a novel therapy for T2DM patients, as its mechanism of action is unique in T2DM patients with minimal adverse effects. This review summarizes the potential of dopamine agonists in the treatment of T2DM.
Topics: Bromocriptine; Cabergoline; Diabetes Mellitus, Type 2; Dopamine Agonists; Humans; Hyperprolactinemia; Parkinson Disease; Restless Legs Syndrome
PubMed: 35486279
DOI: 10.1007/s11356-022-20445-1 -
Revue Neurologique Apr 2019Impulse control disorders (ICDs) in Parkinson's disease (PD) comprise a class of psycho-behavioral disorders often associated with dopamine agonist treatment. The aim of... (Review)
Review
Impulse control disorders (ICDs) in Parkinson's disease (PD) comprise a class of psycho-behavioral disorders often associated with dopamine agonist treatment. The aim of our study was to determine the prevalence of ICDs in a group of Moroccan PD patients and to bring forward some specific aspects in our population. One hundred twenty-five PD patients, without memory impairment and treated for at least six months, were studied. They were questioned about ICDs using the QUIP-RS, and simultaneously evaluated on the motor symptoms and their treatment. Our sample was then divided into two groups: ICDs (+) and ICDs (-) groups. ICDs were identified in 28% of patients: pathological gambling in 3.2%, compulsive sexual behavior in 7.2%, pathological buying in 9.6%, eating behavior disorder in 7.2%, punding-hobbyism in 11.1%. At least two ICDs were found in 14% of patients and dopamine dysregulation syndrome in 10.4%. We also noticed another kind of "ICDs-mimics" specific to our own social context such as "excessive charity" in 18.4%, or excessive reading of the Qur'an in 9.6%. These aspects were not included in the calculation of ICDs prevalence. The ICDs (+) group was younger than the ICDs (-) group (P=0.042) and ICDs were more frequent in men (P=0.031). Dopamine agonist equivalent daily dose (DAED) was significantly higher (P=0.01) in the ICDs (+) group. There are no differences between classes of dopamine agonist used. Young age, male gender and DAED are risk factors for the occurrence of ICDs in Moroccan PD patients, as already described in the DOMINION cohort, but the prevalence found in our study was higher. We highlighted some specific ICDs-mimics in our Arab-Muslim population.
Topics: Adolescent; Adult; Age Factors; Aged; Antiparkinson Agents; Cross-Sectional Studies; Disruptive, Impulse Control, and Conduct Disorders; Dopamine Agonists; Female; Gambling; Humans; Male; Middle Aged; Morocco; Parkinson Disease; Risk Factors; Sex Factors; Sexual Behavior; Young Adult
PubMed: 30935674
DOI: 10.1016/j.neurol.2018.07.009 -
Australasian Psychiatry : Bulletin of... Feb 2018Brexpiprazole is a new dopamine partial agonist antipsychotic in the same class as aripiprazole. This paper will briefly review brexpiprazole and compare it with... (Comparative Study)
Comparative Study Review
OBJECTIVES
Brexpiprazole is a new dopamine partial agonist antipsychotic in the same class as aripiprazole. This paper will briefly review brexpiprazole and compare it with aripiprazole.
CONCLUSIONS
Brexpiprazole and aripiprazole are both partial agonists at dopamine D, and serotonin 5-HT and antagonists at serotonin 5-HT and noradrenergic α receptors. However, the two drugs are significantly different in potencies at various receptors; neurochemical profiles predict that brexpiprazole may be comparable with aripiprazole in its antipsychotic efficacy but may cause less akathisia, extrapyramidal side effects (EPS) and activation. In pivotal trials brexpiprazole demonstrated antipsychotic efficacy in short and long-term studies; it was also found to be an effective adjunct in patients with major depression resistant to antidepressants. Akathisia can occur early in treatment with brexpiprazole, as can minor weight gain and prolactin elevation. Indirect data extrapolations from pivotal studies suggest that brexpiprazole and aripiprazole have comparable efficacy but brexpiprazole may cause less akathisia. Like aripiprazole, brexpiprazole has been approved in the USA for use in schizophrenia and antidepressant-resistant depression. Although much more clinical experience is needed, brexpiprazole appears to be distinct from aripiprazole and a promising new 'metabolically-friendly' antipsychotic option for treatment of psychoses and mood disorders.
Topics: Antipsychotic Agents; Aripiprazole; Depressive Disorder, Treatment-Resistant; Dopamine Agonists; Humans; Quinolones; Schizophrenia; Thiophenes
PubMed: 29017334
DOI: 10.1177/1039856217732473 -
International Review of Neurobiology 2023Although there is no cure for Parkinson's disease (PD), there are several classes of medications with various mechanisms of action that can help improve the...
Although there is no cure for Parkinson's disease (PD), there are several classes of medications with various mechanisms of action that can help improve the functionality of someone with PD. Dopamine derivatives are first line therapies for PD, hence dopamine receptor agonists (DAs) have been shown to improve functionality of symptoms in PD patients. The two main formulations of dopamine agonist medications in PD therapy are ergoline and non-ergoline derivatives. Additionally, it has been shown that PD can involve irregularities in other neurotransmitters, such as acetylcholine, norepinephrine, and serotonin, hence why non-dopaminergic medications are also vital in PD management. Examples include NMDA receptor antagonists, dopamine antagonists (i.e. neuroleptics), acetylcholine receptor antagonists, serotonin receptor 2A agonists, and adenosine A antagonists. In general, dopaminergic medications are the most effective in improving motor involvement with PD, whereas non-dopaminergic medications tend to focus on the non-motor involvement of PD. In this chapter, we will focus on the chemistry and medication background on dopaminergic vs non-dopaminergic therapy, with a focus of adenosine A antagonists at the end.
Topics: Humans; Parkinson Disease; Dopamine; Dopamine Agonists; Acetylcholine; Adenosine
PubMed: 37741688
DOI: 10.1016/bs.irn.2023.06.004 -
Seminars in Neurology Apr 2017Impulsive and compulsive behaviors in Parkinson's disease (PD) patients are most often attributed to dopamine agonist therapy; dysregulation of the mesocorticolimbic... (Review)
Review
Impulsive and compulsive behaviors in Parkinson's disease (PD) patients are most often attributed to dopamine agonist therapy; dysregulation of the mesocorticolimbic system accounts for this behavioral phenotype. The clinical presentation is commonly termed (ICD): Behaviors include hypersexuality, compulsive eating, shopping, pathological gambling, and compulsive hobby participation. However, not all PD individuals taking dopamine agonists develop these behavioral changes. In this review, the authors focus on the similarities between the phenotypic presentation of ICDs with that of other reward-based behavioral disorders, including binge eating disorder, pathological gambling, and substance use disorders. With this comparison, we emphasize that the transition from an impulsive to compulsive behavior likely follows a ventral to dorsal striatal pattern, where an altered dopaminergic reward system underlies the emergence of these problematic behaviors. The authors discuss the neurobiological similarities between these latter disorders and ICDs, emphasizing similar pathophysiological processes and discussing treatment options that have potential for translation to PD patients.
Topics: Disruptive, Impulse Control, and Conduct Disorders; Dopamine; Dopamine Agonists; Humans; Impulsive Behavior; Parkinson Disease
PubMed: 28511259
DOI: 10.1055/s-0037-1601887 -
Neurotherapeutics : the Journal of the... Oct 2020Parkinson disease (PD), as a slowly progressive neurodegenerative disorder, undergoes six neuropathological stages. The earliest clinical manifestation presents in the... (Review)
Review
Parkinson disease (PD), as a slowly progressive neurodegenerative disorder, undergoes six neuropathological stages. The earliest clinical manifestation presents in the middle stage of the disorder pathologically, when 50% or more of the dopaminergic neurons have degenerated in the substantia nigra. This discrepancy between the early stage clinically and that pathologically has, in part, spurred the debate as to when it is best to initiate symptomatic therapy. The most well-studied monotherapeutic agents for PD in its early course include levodopa (the cornerstone of PD therapy), dopamine agonists, and monoamine oxidase inhibitors (MAOIs). With several options for initiating pharmacologic therapy, along with the heterogenous presentation of the disorder, an individualized approach is warranted. Careful deliberation must be done to optimize risk reduction while providing effective symptom control, taking the chronological age, comorbidities, social and financial disposition, work status, and both immediate- and long-term goals into consideration. Generally, treatment can be delayed in patients with mild symptoms and minimal functional impairment at any age. If treatment must be initiated, dopamine agonists and monoamine oxidase type B inhibitors can be used, especially in younger patients with milder disease. However, for older patients, those with moderate to severe PD symptoms, regardless of age, or for patients with greater comorbidities, levodopa generally remains the better choice. Eventually, regardless of initial therapy, studies have shown that most will eventually require levodopa therapy when symptoms become more disabling.
Topics: Antiparkinson Agents; Dopamine Agonists; Early Diagnosis; Humans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Treatment Outcome
PubMed: 32935299
DOI: 10.1007/s13311-020-00924-4 -
Movement Disorders : Official Journal... Mar 2021No clinical trials have been specifically designed to compare medical treatments after surgery in Parkinson's disease (PD). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
No clinical trials have been specifically designed to compare medical treatments after surgery in Parkinson's disease (PD).
OBJECTIVE
Study's objective was to compare the efficacy and safety of levodopa versus dopamine agonist monotherapy after deep brain stimulation (DBS) in PD.
METHODS
Thirty-five surgical candidates were randomly assigned to receive postoperative monotherapy with either levodopa or dopamine agonist in a randomized, single-blind study. All patients were reevaluated in short- (3 months), mid- (6 months), and long-term (2.5 years) follow-up after surgery. The primary outcome measure was the change in the Non-Motor Symptoms Scale (NMSS) 3 months after surgery. Secondary outcome measures were the percentage of patients maintaining monotherapy, change in motor symptoms, and specific non-motor symptoms (NMS). Analysis was performed primarily in the intention-to-treat population.
RESULTS
Randomization did not significantly affect the primary outcome (difference in NMSS between treatment groups was 4.88 [95% confidence interval: -11.78-21.53, P = 0.566]). In short- and mid-term follow-up, monotherapy was safe and feasible in more than half of patients (60% in short- and 51.5% in mid-term follow-up), but it was more often possible for patients on levodopa. The ability to maintain dopamine agonist monotherapy was related to optimal contact location. In the long term, levodopa monotherapy was feasible only in a minority of patients (34.2%), whereas dopamine agonist monotherapy was not tolerated due to worsening of motor conditions or occurrence of impulse control disorders.
CONCLUSIONS
This trial provides evidence for simplifying pharmacological treatment after functional neurosurgery for PD. The reduction in dopamine receptor agonists should be attempted while monitoring for occurrence of NMSs, such as apathy and sleep disturbances. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Antiparkinson Agents; Deep Brain Stimulation; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Single-Blind Method; Treatment Outcome
PubMed: 33165964
DOI: 10.1002/mds.28382 -
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