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Pituitary Feb 2020Treatment goals in prolactinomas are to correct hypogonadism, restore fertility and control tumor mass in case of macroadenomas. According to current guidelines, medical... (Review)
Review
PURPOSE
Treatment goals in prolactinomas are to correct hypogonadism, restore fertility and control tumor mass in case of macroadenomas. According to current guidelines, medical treatment of asymptomatic postmenopausal women is not indicated. The purpose of this study was to review the current literature pertaining to biological behavior of prolactinomas during menopause, likelihood of successful dopamine agonist withdrawal during this period and possible prolactin-mediated increased morbidity that could modify current management.
METHODS
A comprehensive literature search including papers published until July 2019 was conducted using PubMed and Medline databases.
RESULTS
Women with prolactinomas entering menopause have a higher chance of prolactin normalization of treatment compared with women in their reproductive years. Although most prolactin secreting adenomas diagnosed during menopause are large, they respond well to dopamine agonist treatment. Data directly linking hyperprolactinemia with an increased risk of cancer and cardiovascular and metabolic morbidity are inconsistent. There is no data indicating that correction of hyperprolactinemia improves clinical outcomes in asymptomatic patients bearing microadenomas.
CONCLUSION
There is no evidence that justifies changing current recommendations to withhold medical treatment of microprolactinomas in asymptomatic post-menopausal women. Macroprolactinoma patients should be treated according to standard clinical practice.
Topics: Dopamine Agonists; Female; Humans; Hypogonadism; Menopause; Prolactin; Prolactinoma
PubMed: 31686376
DOI: 10.1007/s11102-019-00998-0 -
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 -
Dopamine Agonist Cotreatment Alters Neuroplasticity and Pharmacology of Levodopa-Induced Dyskinesia.Movement Disorders : Official Journal... Mar 2023Current models of levodopa (L-dopa)-induced dyskinesia (LID) are obtained by treating dopamine-depleted animals with L-dopa. However, patients with LID receive...
BACKGROUND
Current models of levodopa (L-dopa)-induced dyskinesia (LID) are obtained by treating dopamine-depleted animals with L-dopa. However, patients with LID receive combination therapies that often include dopamine agonists.
OBJECTIVE
Using 6-hydroxydopamine-lesioned rats as a model, we aimed to establish whether an adjunct treatment with the D2/3 agonist ropinirole impacts on patterns of LID-related neuroplasticity and drug responses.
METHODS
Different regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment were compared using measures of hypokinesia and dyskinesia. Striatal expression of ∆FosB and angiogenesis markers were studied immunohistochemically. Antidyskinetic effects of different drug categories were investigated in parallel groups of rats receiving either L-dopa monotreatment or L-dopa combined with ropinirole.
RESULTS
We defined chronic regimens of L-dopa monotreatment and L-dopa-ropinirole cotreatment inducing overall similar abnormal involuntary movement scores. Compared with the monotreatment group, animals receiving the L-dopa-ropinirole combination exhibited an overall lower striatal expression of ∆FosB with a distinctive compartmental distribution. The expression of angiogenesis markers and blood-brain barrier hyperpermeability was markedly reduced after L-dopa-ropinirole cotreatment compared with L-dopa monotreatment. Moreover, significant group differences were detected upon examining the response to candidate antidyskinetic drugs. In particular, compounds modulating D1 receptor signaling had a stronger effect in the L-dopa-only group, whereas both amantadine and the selective NMDA antagonist MK801 produced a markedly larger antidyskinetic effect in L-dopa-ropinirole cotreated animals.
CONCLUSIONS
Cotreatment with ropinirole altered LID-related neuroplasticity and pharmacological response profiles. The impact of adjuvant dopamine agonist treatment should be taken into consideration when investigating LID mechanisms and candidate interventions in both clinical and experimental settings. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Topics: Rats; Animals; Levodopa; Dopamine Agonists; Antiparkinson Agents; Rats, Sprague-Dawley; Dyskinesia, Drug-Induced; Oxidopamine; Disease Models, Animal
PubMed: 36656044
DOI: 10.1002/mds.29301 -
Biomolecules May 2023Current pharmacotherapy has limited efficacy and/or intolerable side effects in late-stage Parkinson's disease (LsPD) patients whose daily life depends primarily on... (Randomized Controlled Trial)
Randomized Controlled Trial
Current pharmacotherapy has limited efficacy and/or intolerable side effects in late-stage Parkinson's disease (LsPD) patients whose daily life depends primarily on caregivers and palliative care. Clinical metrics inadequately gauge efficacy in LsPD patients. We explored if a D dopamine agonist would have efficacy in LsPD using a double-blind placebo-controlled crossover phase Ia/b study comparing the D agonist PF-06412562 to levodopa/carbidopa in six LsPD patients. Caregiver assessment was the primary efficacy measure because caregivers were with patients throughout the study, and standard clinical metrics inadequately gauge efficacy in LsPD. Assessments included standard quantitative scales of motor function (MDS-UPDRS-III), alertness (Glasgow Coma and Stanford Sleepiness Scales), and cognition (Severe Impairment and Frontal Assessment Batteries) at baseline (Day 1) and thrice daily during drug testing (Days 2-3). Clinicians and caregivers completed the clinical impression of change questionnaires, and caregivers participated in a qualitative exit interview. Blinded triangulation of quantitative and qualitative data was used to integrate findings. Neither traditional scales nor clinician impression of change detected consistent differences between treatments in the five participants who completed the study. Conversely, the overall caregiver data strongly favored PF-06412562 over levodopa in four of five patients. The most meaningful improvements converged on motor, alertness, and functional engagement. These data suggest for the first time that there can be useful pharmacological intervention in LsPD patients using D agonists and also that caregiver perspectives with mixed method analyses may overcome limitations using methods common in early-stage patients. The results encourage future clinical studies and understanding of the most efficacious signaling properties of a D agonist for this population.
Topics: Humans; Parkinson Disease; Levodopa; Dopamine Agonists; Antiparkinson Agents; Dopamine
PubMed: 37238699
DOI: 10.3390/biom13050829 -
Archives of Medical Research Dec 2023Prolactinomas are the most common functional pituitary tumors, accounting for 40% of all pituitary adenomas. Medical treatment with dopamine agonists (DA), mainly... (Review)
Review
Prolactinomas are the most common functional pituitary tumors, accounting for 40% of all pituitary adenomas. Medical treatment with dopamine agonists (DA), mainly cabergoline, is considered the primary therapy for these patients. Prolactin normalization is achieved in 80-90% of prolactinomas treated with cabergoline. Patients resistant to the standard dose can escalate the dose of cabergoline up to the maximum tolerated dose. The expression of dopamine (D2) receptors and dopamine affinity is decreased in aggressive and resistant prolactinomas. Patients with aggressive and DA-resistant adenomas or with rare PRL-secreting carcinomas can be treated off-label with temozolomide (TMZ), a DNA alkylating agent. TMZ is effective in 40-50% of treated lactotroph tumors showing at least a partial response. However, patients tend to escape from the effect of TMZ after a limited time of response. Other therapeutic options include aromatase inhibitors, the somatostatin receptor ligand pasireotide, peptide receptor radionuclide therapy (PRRT), immune-checkpoint inhibitors, tyrosine-kinase inhibitors, or everolimus, the mammalian target of rapamycin inhibitor. These experimental treatments were effective in some patients carrying refractory prolactinomas showing usually partial tumor control. However, the number of treated patients with any of these new therapeutic options is very limited and treatment results are inconsistent, thus additional experience with more patients is required.
Topics: Humans; Prolactinoma; Dopamine Agonists; Cabergoline; Dopamine; Pituitary Neoplasms; Temozolomide; Prolactin
PubMed: 37689507
DOI: 10.1016/j.arcmed.2023.102883 -
Current Pharmaceutical Design 2020Rotigotine is a non-ergoline, high lipophilic dopamine agonist. It is indicated as the first-line therapy for Parkinson's disease (PD) and Restless Leg Syndrome (RLS).... (Review)
Review
Rotigotine is a non-ergoline, high lipophilic dopamine agonist. It is indicated as the first-line therapy for Parkinson's disease (PD) and Restless Leg Syndrome (RLS). However, the precise mechanism of rotigotine is yet to be known. Rotigotine has similar safety and tolerability to the other oral non-ergolinic dopamine antagonists in clinical trials, which include nausea, dizziness and somnolence. Neupro® was the first marketed transdermal patch formulation having rotigotine. The transdermal delivery system is advantageous as it enables continuous administration of the drug, thus providing steady-state plasma drug concentration for 24-hours. Intranasal administration of rotigotine allows the drug to bypass the blood-brain barrier enabling it to reach the central nervous system within minutes. Rotigotine can also be formulated as an extended-release microsphere for injection. Some challenges remain in other routes of rotigotine administration such as oral, parenteral and pulmonary, whereby resolving these challenges will be beneficial to patients as they are less invasive and comfortable in terms of administration. This review compiles recent work on rotigotine delivery, challenges and its future perspective.
Topics: Administration, Cutaneous; Dopamine Agonists; Humans; Restless Legs Syndrome; Tetrahydronaphthalenes; Thiophenes
PubMed: 32175832
DOI: 10.2174/1381612826666200316154300 -
Brain and Nerve = Shinkei Kenkyu No... May 2023Restless legs syndrome (RLS) is a neurological disorder that causes insomnia and daytime functional disability due to an urge to move the legs usually accompanied by...
Restless legs syndrome (RLS) is a neurological disorder that causes insomnia and daytime functional disability due to an urge to move the legs usually accompanied by uncomfortable sensations. Non-pharmacologic treatment includes regular sleep habits and exercise. Iron supplementation is indicated for patients with low serum ferritin levels. Antidepressants, antihistaminergics, and dopamine antagonists should be reduced or discontinued because they induce RLS symptoms. Dopamine agonists and alpha 2-delta ligands are the first-line pharmacological treatments for RLS.
Topics: Humans; Restless Legs Syndrome; Dopamine Agonists; Sleep
PubMed: 37194531
DOI: 10.11477/mf.1416202378 -
Pituitary Feb 2020Renewed interest in transsphenoidal surgery (TSS) as a therapeutic option for prolactinomas has emerged. (Review)
Review
PURPOSE
Renewed interest in transsphenoidal surgery (TSS) as a therapeutic option for prolactinomas has emerged.
METHODS
Based on contemporary literature and own experience, the changing role of surgery for treatment of prolactinomas is discussed.
RESULTS
Today, TSS is performed by minimally invasive microscopic or endoscopic techniques. Normoprolactinemia is obtained in 71-100% of patients with microprolactinomas by TSS. Almost equal results are found in circumscribed intrasellar macroprolactinomas. In experienced hands, pituitary function is preserved in TSS. The risk of cardiac valve disease is still a concern with ergot-derived dopamine-agonists (DAs) in patients requiring long-term, high-dose dopamine-agonist (DA) treatment. Cost-utility analysis favors TSS over DA treatment. The possible negative impact of DA treatment on future surgical results is still a controversial and unsettled issue. In patients who wish to become pregnant, the advantages of microprolactinoma removal to avoid DAs and macroprolactinoma debulking to avoid symptomatic enlargement during pregnancy should be discussed with the patients. Young patients' age is an argument for surgery to circumvent the unpredictable sequelae of long-term DA treatment. Surgery should be discussed in male gender because of a higher likelihood of DA resistance and aggressive behavior of prolactinoma.
CONCLUSION
Given excellent results of TSS and concerns about medical treatment, the scale of indications for TSS as an alternative to DAs has increased. The patient's wishes concerning a chance at a cure with TSS instead of a long-term treatment with DAs has become an important and accepted indication. With DA medication and TSS, two effective treatment modalities for prolactinomas are available that can be used in a complementary fashion.
Topics: Dopamine Agonists; Female; Humans; Male; Prolactinoma; Treatment Outcome
PubMed: 31853793
DOI: 10.1007/s11102-019-01016-z -
Neurogastroenterology and Motility May 2021Dopamine receptor 2 (DRD2) and ghrelin receptor (GHSR1a) agonists both stimulate defecation by actions at the lumbosacral defecation center. Dopamine is in nerve...
BACKGROUND
Dopamine receptor 2 (DRD2) and ghrelin receptor (GHSR1a) agonists both stimulate defecation by actions at the lumbosacral defecation center. Dopamine is in nerve terminals surrounding autonomic neurons of the defecation center, whereas ghrelin is not present in the spinal cord. Dopamine at D2 receptors generally inhibits neurons, but at the defecation center, its effect is excitatory.
METHODS
In vivo recording of defecation and colorectal propulsion was used to investigate interaction between DRD2 and GHSR1a. Localization studies were used to determine sites of receptor expression in rat and human spinal cord.
KEY RESULTS
Dopamine, and the DRD2 agonist, quinpirole, directly applied to the lumbosacral cord, caused defecation. The effect of intrathecal dopamine was inhibited by the GHSR1a antagonist, YIL781, given systemically, but YIL781 was not an antagonist at DRD2. The DRD2 agonist, pramipexole, administered systemically caused colorectal propulsion that was prevented when the pelvic nerves were cut. Drd2 and Ghsr were expressed together in autonomic preganglionic neurons at the level of the defecation centers in rat and human. Behaviorally induced defecation (caused by water avoidance stress) was reduced by the DRD2 antagonist, sulpiride. We had previously shown it is reduced by YIL781.
CONCLUSIONS AND INFERENCES
Our observations imply that dopamine is a transmitter of the defecation pathways whose actions are exerted through interacting dopamine (D2) and ghrelin receptors on lumbosacral autonomic neurons that project to the colorectum. The results explain the excitation by dopamine agonists and the conservation of GHSR1a in the absence of ghrelin.
Topics: Animals; Defecation; Dopamine; Dopamine Agonists; Dopamine Antagonists; Gastrointestinal Motility; Ghrelin; Humans; Piperidines; Pramipexole; Quinazolinones; Quinpirole; Rats; Receptors, Dopamine D2; Receptors, Ghrelin; Spinal Cord; Spinal Cord Lateral Horn; Sulpiride
PubMed: 33264473
DOI: 10.1111/nmo.14051 -
Biomedicine & Pharmacotherapy =... May 2022Advances in molecular biology and biochemistry have improved the treatment of Parkinson's disease (PD). There has been extensive evidence on the benefit of standard... (Review)
Review
Advances in molecular biology and biochemistry have improved the treatment of Parkinson's disease (PD). There has been extensive evidence on the benefit of standard treatment (e.g., deep brain stimulation, levodopa, and dopamine agonists) and acupuncture for PD. This article aims to distill the similarities and differences in the treatment concepts between Chinese and Western medicine from the perspective of reinforcing the deficiency and purging the excess, summarize the latest evidence on the benefits of acupuncture for PD from theory to practice, and propose prospective treatment options for PD.
Topics: Acupuncture Therapy; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Prospective Studies
PubMed: 35366533
DOI: 10.1016/j.biopha.2022.112907