-
Journal of Neural Transmission (Vienna,... Sep 2022The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan... (Review)
Review
The trajectory of the use of dopamine replacement therapy (DRT) in Parkinson's disease (PD) is variable and doses may need to be increased, but also tapered. The plan for dose adjustment is usually done as per drug information recommendations from the licensing bodies, but there are no clear guidelines with regards to the best practice regarding the tapering off schedule given sudden dose reductions of drugs such as dopamine agonists may have serious adverse consequences. A systematic literature search was, therefore, performed to derive recommendations and the data show that there are no controlled studies or evidence-based recommendations how to taper or discontinue PD medication in a systematic manner. Most of the data were available on the dopamine agonist withdrawal syndrome (DAWS) and we found only two instructions on how to reduce pramipexole and rotigotine published by the EMA. We suggest that based on the available data, levodopa, dopamine agonists (DA), and amantadine should not be discontinued abruptly. Abrupt or sudden reduction of DA or amantadine in particular can lead to severe life-threatening withdrawal symptoms. Tapering off levodopa, COMT inhibitors, and MAO-B inhibitors may worsen motor and non-motor symptoms. Based on our clinical experience, we have proposed how to reduce PD medication and this work will form the basis of a future Delphi panel to define the recommendations in a consensus.
Topics: Amantadine; Dopamine; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Substance Withdrawal Syndrome
PubMed: 34324057
DOI: 10.1007/s00702-021-02389-x -
Journal of Psychopharmacology (Oxford,... Mar 2021Cariprazine is a dopamine D-preferring D/D receptor partial agonist compound recently introduced to treat schizophrenia and bipolar disorder. Although cariprazine is...
BACKGROUND
Cariprazine is a dopamine D-preferring D/D receptor partial agonist compound recently introduced to treat schizophrenia and bipolar disorder. Although cariprazine is clinically classified as a low-somnolence drug, to date no detailed polysomnographic study is available on its effect on sleep.
AIMS
This study examined the acute systemic effects of cariprazine on the rat sleep architecture and electroencephalography spectral power.
METHODS
Sprague Dawley rats were recorded during their normal sleep period for four hours, and their sleep stages were classified.
RESULTS
Cariprazine (0.3 mg/kg i.p.) reduced the time spent in rapid eye movement (REM) sleep and increased REM latency. This dose of cariprazine decreased the gamma (40-80 Hz) band frequency oscillations and increased the theta (4-9 Hz) and alpha (9-15 Hz) frequencies during the wake periods but not during slow-wave sleep. The 0.03 mg/kg dose of cariprazine only increased the alpha power during the wake periods, while the 0.003 mg/kg dose was without any effect.
CONCLUSION
Taken together, the present results suggest that the REM-suppressing effect of cariprazine may be related to its effectiveness in improving depressive symptoms, as various drugs with similar REM-reducing properties effectively treat the depressive state, whereas the gamma power-reducing effect of cariprazine may be indicative of its efficacy in schizophrenia or mania, as similar effects have been observed with other D and 5-HT receptor antagonist drugs. These data contribute to our understanding of the complex mechanism of action that may stand behind the clinical efficacy of cariprazine.
Topics: Animals; Antipsychotic Agents; Dopamine Agonists; Electroencephalography; Male; Piperazines; Rats; Rats, Sprague-Dawley; Sleep; Sleep, REM
PubMed: 33406962
DOI: 10.1177/0269881120981378 -
Expert Review of Neurotherapeutics Sep 2020Dopamine agonists have been widely used to treat patients with Parkinson's disease, but concerns related to their well-known side effects might prevent their use even... (Review)
Review
INTRODUCTION
Dopamine agonists have been widely used to treat patients with Parkinson's disease, but concerns related to their well-known side effects might prevent their use even when indicated. In this review, the authors describe for the first time the concept of 'Dopamine Agonist Phobia', a pharmacophobia that the authors believe might affect clinicians, and they provide evidence of the benefits of dopamine agonists, focusing on non-motor symptoms.
AREAS COVERED
The authors performed an extensive literature research, including studies exploring the use of dopamine agonists for the treatment of non-motor symptoms. The authors indicate the highest level of evidence in each section.
EXPERT OPINION
'Dopamine Agonist Phobia' may preclude valid therapeutic options in selected cases, specifically for the treatment of non-motor symptoms. Thus, the authors propose a personalized approach in Parkinson's disease treatment, and encourage a thoughtful use of dopamine agonists, rather than an overall nihilism.
Topics: Dopamine Agonists; Drug Prescriptions; Humans; Parkinson Disease; Practice Patterns, Physicians'
PubMed: 32755243
DOI: 10.1080/14737175.2020.1806059 -
The Canadian Journal of Neurological... Sep 2023
Topics: Humans; Dopamine Agonists; Parkinson Disease; Suicide; Substance Withdrawal Syndrome; Disruptive, Impulse Control, and Conduct Disorders; Antiparkinson Agents
PubMed: 35801613
DOI: 10.1017/cjn.2022.272 -
International Immunopharmacology Nov 2020Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. Dopamine is an important...
Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by progressive cognitive dysfunction and memory impairment. Dopamine is an important catecholaminergic neurotransmitter that controls movement, reward, motivation, and cognition. Recently, dopamine receptors were reported to regulate immune system in both periphery and central nervous system. However, whether dopamine D1 receptor (DRD1) activation could improve neuroinflammation in AD conditions remains unknown. The present study aimed to investigate the therapeutic effects and underlying mechanisms of a potent and selective DRD1 agonist A-68930 on Aβ-induced mice. Here we showed that intraperitoneal injection of A-68930 significantly ameliorated Aβ-induced cognitive dysfunction in mice. Moreover, both in vivo and in vitro data showed that A-68930-induced DRD1 activation significantly inhibited NLRP3 inflammasome-dependent neuroinflammation induced by Aβ, and this effect may be mediated by the activation of AMPK/autophagy signaling pathway, which enhanced NLRP3 inflammasome degradation and thus decreased the secretion of IL-1β and IL-18. The present study suggests that A-68930-induced DRD1 signaling efficiently alleviates Aβ-induced cognitive impairment and neuroinflammation in mice and BV2 cells, and DRD1 may become a promising therapeutic target for AD.
Topics: Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents; Cell Line; Cerebral Cortex; Chromans; Cognitive Dysfunction; Cytokines; Dopamine Agonists; Encephalitis; Hippocampus; Male; Mice, Inbred ICR; Neurodegenerative Diseases; Neurons; Peptide Fragments
PubMed: 33182028
DOI: 10.1016/j.intimp.2020.106963 -
Pituitary Feb 2020Prolactinomas are the most common pituitary tumors and pathological hyperprolactinemia. Therefore, women harboring prolactinomas frequently present infertility due to... (Review)
Review
Prolactinomas are the most common pituitary tumors and pathological hyperprolactinemia. Therefore, women harboring prolactinomas frequently present infertility due to the gonadal axis impairment. The gold-standard treatment is dopamine agonist (DA) which can reverse hyperprolactinemia and hypogonadism, and promote tumor shrinkage in the majority of cases. Therefore, reports of pregnancy in such cohort become more common. In this scenario, bromocriptine is still the DA of choice due to its shorter half-life and larger experience as compared to cabergoline. In DA resistant cases, transsphenoidal pituitary surgery is indicated. However, potential risks of DA-induced pregnancies include fetal exposition and symptomatic tumor growth. Dopamine agonist should be discontinued as soon as pregnancy is confirmed in microprolactinomas and intrasellar macroprolactinomas (MAC). Concerning expansive/invasive MAC, DA maintenance should be considered. Periodically clinical evaluation should be performed during pregnancy, being sellar imaging indicated if tumor symptomatic growth is suspected. In such cases, if DA treatment fails, neurosurgery is indicated.
Topics: Bromocriptine; Dopamine Agonists; Female; Humans; Pituitary Neoplasms; Pregnancy; Prolactinoma
PubMed: 31792668
DOI: 10.1007/s11102-019-01010-5 -
Pituitary Feb 2020Dopamine agonists (DAs) are well recognized as the first-line therapy for prolactinomas due to their efficacy in achieving tumoral shrinkage and normoprolactinemia.... (Review)
Review
Dopamine agonists (DAs) are well recognized as the first-line therapy for prolactinomas due to their efficacy in achieving tumoral shrinkage and normoprolactinemia. However, it remains to be established the best timing to withdraw DAs and in which patients this should be attempted. Studies in the 1980s, mainly using bromocriptine, started to defy the concept that DAs should be regarded as a lifelong therapy considering that sustained normoprolactinemia was attained in a small subset of patients after drug withdrawal. The introduction of the more effective agent cabergoline led to an increase in the percentages of remission. The most recent meta-analysis on the topic stated than remission rates after withdrawal can range from 15% in macroprolactinoma patients treated with bromocriptine to 41% in those with microprolactinomas previously treated with cabergoline. When more stringent criteria were applied before attempting withdrawal, sustained remission ensued in more than 50% of the individuals. Treatment duration for more than 24 months, the achievement of normoprolactinemia, marked reduction (≥ 50%) in tumoral size and DAs tapering till a low maintenance dose (e.g. cabergoline 0.5 mg/week) have been the most consistently identified predictors of success. In addition, a growing amount of evidence suggests that the post-pregnancy/breastfeeding period and menopause are reasonable timings to re-access the need for continuing DAs therapy. Considering that the achievement of sustained normoprolactinemia is still far from being universal after the withdrawal, even in highly selected cohorts, future larger prospective studies should continue to address this issue.
Topics: Cabergoline; Dopamine Agonists; Female; Humans; Male; Prolactinoma
PubMed: 31556013
DOI: 10.1007/s11102-019-00989-1 -
Drug Resistance Updates : Reviews and... Mar 2024The treatment of dopamine agonists (DA) resistant prolactinomas remains a formidable challenge, as the mechanism of resistance is still unclear, and there are currently...
BACKGROUND
The treatment of dopamine agonists (DA) resistant prolactinomas remains a formidable challenge, as the mechanism of resistance is still unclear, and there are currently no viable alternative drug therapies available. This study seeks to investigate the mechanism of DA resistance in prolactinomas and identify new potentially effective drugs.
METHODS
To explore the mechanism of DA resistance in prolactinomas, this study conducted transcriptome sequencing analysis on 27 cases of DA-resistant prolactinomas and 10 cases of sensitive prolactinomas. In addition, single-cell sequencing analysis was performed on 3 cases of DA-resistant prolactinomas and 3 cases of sensitive prolactinomas. Furthermore, to screen for potential therapeutic drugs, the study successfully established an organoids model for DA-resistant prolactinomas and screened 180 small molecule compounds using 8 organoids. The efficacy of the identified drugs was verified through various assays, including CCK-8, colony formation, CTG, and flow cytometry, and their mechanisms of action were confirmed through WB and IHC. The effectiveness of the identified drugs was evaluated both in vitro and in vivo.
RESULTS
The results of transcriptome sequencing and single-cell sequencing analyses showed that DA resistance in prolactinomas is associated with the upregulation of the Focal Adhesion (FA) signaling pathway. Additionally, immunohistochemical validation revealed that FAK and Paxillin were significantly upregulated in DA-resistant prolactinomas. Screening of 180 small molecule compounds using 8 organoids identified Genistein as a potentially effective drug for DA-resistant prolactinomas. Experimental validation demonstrated that Genistein inhibited the proliferation of pituitary tumor cell lines and organoids and promoted apoptosis in pituitary tumor cells. Moreover, both the cell sequencing results and WB validation results of the drug-treated cells indicated that Genistein exerts its anti-tumor effect by inhibiting the FA pathway. In vivo, experiments also showed that Genistein can inhibit subcutaneous tumor formation.
CONCLUSION
DA resistance in prolactinomas is associated with upregulation of the Focal Adhesion (FA) signaling pathway, and Genistein can exert its anti-tumor effect by inhibiting the expression of the FA pathway.
Topics: Humans; Pituitary Neoplasms; Dopamine Agonists; Prolactinoma; Prolactin; Genistein; Neuroendocrine Tumors; Drug Resistance, Neoplasm
PubMed: 38277755
DOI: 10.1016/j.drup.2024.101056 -
BMC Research Notes Sep 2022There are conflicting data regarding the relationship between Parkinson's disease (PD) and the atherosclerotic process. This study aimed to compare endothelial function...
OBJECTIVE
There are conflicting data regarding the relationship between Parkinson's disease (PD) and the atherosclerotic process. This study aimed to compare endothelial function in patients with PD and matched controls. In PD subjects, we searched for factors contributing to endothelial dysfunction as well. Traditional vascular risk factors, PD characteristics, and PD medication were considered.
RESULTS
We prospectively enrolled 41 patients with PD and 41 controls matched for age, sex, body mass index, and vascular risk factors. Endothelial function (EF) was assessed using peripheral arterial tonometry (EndoPAT 2000 device) and expressed as reperfusion hyperemia index (RHI). Clinical characteristics including PD medication were recorded. RHI was non-significantly lower in the PD group than in controls (1.8 ± 0.5 vs. 1.9 ± 0.5, p = 0.478). In PD patients, in linear regression analysis, smoking (beta = -0.453, p = 0.008) and use of dopamine agonists (beta = -0.365, p = 0.030) were significant contributors in a model predicting RHI. Despite non-significant differences in endothelial dysfunction between PD patients and controls, our results suggest an association between smoking, dopamine agonists, and impaired EF in PD patients. The small sample size, as well as the absence of an extended search for traditional and non-traditional vascular risk factors, are the most important factors limiting the interpretation of the current results.
Topics: Dopamine Agonists; Endothelium, Vascular; Humans; Hyperemia; Parkinson Disease; Risk Factors
PubMed: 36064624
DOI: 10.1186/s13104-022-06176-z -
Neurological Sciences : Official... Jul 2021A significant proportion of patients with Parkinson's disease (PD) display a set of impulsive-compulsive behaviors at some point during the course of illness. These... (Review)
Review
INTRODUCTION
A significant proportion of patients with Parkinson's disease (PD) display a set of impulsive-compulsive behaviors at some point during the course of illness. These behaviors range from the so-called behavioral addictions to dopamine dysregulation syndrome, punding and hoarding disorders. These behaviors have been consistently linked to the use of dopaminergic medications used to treat PD motor symptoms (dopamine agonists, levodopa, and other agents) and less consistently to neuromodulation techniques such as deep brain stimulation (DBS). Since there are still no approved treatments for these conditions, their pharmacological management is still a big challenge for clinicians.
METHODS
We conducted an extensive review of current pharmacological and neuromodulation literature for the management of impulsive-compulsive disorders in PD patients.
RESULTS
Pharmacological treatment approaches for impulsive-compulsive behaviors and DDS in PD patients include reduction of levodopa (LD), reduction/cessation of dopamine agonist (DA), and initiation of infusion therapies (apomorphine infusion and duodopa). Also, atomoxetine, a noradrenergic agent approved for the treatment of attention deficit hyperactivity disorder, showed some interesting preliminary results but there is still a lack of controlled longitudinal studies. Finally, while DBS effects on impulsive-compulsive disorders are still controversial, non-invasive techniques (such as transcranial magnetic stimulation and transcranial direct current stimulation) could have a potential positive effect but, again, there is still a lack of controlled trials.
CONCLUSION
Managing impulsivity and compulsivity in PD patients is still a non-evidence-based challenge for clinicians. Controlled trials on promising approaches such as atomoxetine and non-invasive neuromodulation techniques are needed.
Topics: Compulsive Behavior; Disruptive, Impulse Control, and Conduct Disorders; Dopamine Agonists; Humans; Impulsive Behavior; Parkinson Disease; Transcranial Direct Current Stimulation
PubMed: 33852081
DOI: 10.1007/s10072-021-05237-8