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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 -
Expert Review of Endocrinology &... May 2019Prolactinomas represent the most common pituitary adenomas encountered in the clinic. While a majority of these tumors will be successfully treated by dopamine agonist... (Review)
Review
INTRODUCTION
Prolactinomas represent the most common pituitary adenomas encountered in the clinic. While a majority of these tumors will be successfully treated by dopamine agonist (DA) such as cabergoline, their management becomes problematic since a resistance to DA can occur and/or if the tumor displays features of aggressiveness, two conditions that are closely related.
AREAS COVERED
Epidemiology and medical treatment of prolactinomas; resistance to DA and molecular basis of DA-resistance; therapeutical alternatives in case of DA-resistant Prolactinomas and therapies in development; summarizing conclusions.
EXPERT OPINION
The management of DA-resistant prolactinomas requires a multidisciplinary approach by an expert team. Along with discussions about surgery with or without gamma knife radiosurgery, genetic screening for multiple endocrine neoplasia type 1 (MEN1) syndrome is actively discussed in a case-by-case approach. In case of surgery, a careful analysis of the tumor sample can provide information about its aggressivity potential according to recent criteria. Ultimately, temozolomide can be indicated if the tumor is rapidly growing and/or threatening for the patient.
Topics: Disease Management; Dopamine Agonists; Drug Resistance, Neoplasm; Humans; Pituitary Neoplasms; Prolactinoma; Signal Transduction; Treatment Outcome
PubMed: 30913932
DOI: 10.1080/17446651.2019.1596024 -
Psychiatry and Clinical Neurosciences Mar 2023Impulse control disorders (e.g. pathological gambling, hypersexuality) may develop as adverse reactions to drugs. Pathogenetic hypotheses have mainly focused on...
INTRODUCTION
Impulse control disorders (e.g. pathological gambling, hypersexuality) may develop as adverse reactions to drugs. Pathogenetic hypotheses have mainly focused on D3-receptor agonism, and switching to alternatives with different pharmacologic mechanisms represents a common management strategy. Nonetheless, treatment failure is common and gaining pathophysiological insights is needed.
AIM
We aimed to identify targets potentially contributing to pathologic impulsivity.
METHOD
We performed a pharmacovigilance-pharmacodynamic study on dopamine agonists and antipsychotics using the Food and Drug Administration Adverse Event Reporting System (January 2004-December 2021). We estimated disproportionate reporting using the Bayesian information component. Using online public databases (IUPHAR, ChEMBL, PDSP, DrugBank), we calculated drug occupancies. To identify the targets potentially contributing to impulsivity, we fitted univariate regression models interpolating information components and occupancies within dopamine agonists and antipsychotics. Sensitivity analyses were performed to check for the robustness of the results.
RESULTS
Among 19 887 reports of impulsivity, 5898 recorded an antipsychotic, and 3100 a dopamine agonist. The more robust signals concerned aripiprazole (N = 3091; median information component [95% confidence interval] = 4.51[4.45-4.55]) and brexpiprazole (229; 4.00[3.78-4.16]) for antipsychotics, pergolide (105; 5.82[5.50-6.06]) and pramipexole (2009; 5.43[5.36-5.48]) for dopamine agonists. Robust, significant positive associations between drug occupancy and impulsivity reporting were found for D3 within dopamine agonists (beta = 1.52; P-value = 0.047) and 5-HT1a within antipsychotics (1.92, 0.029).
CONCLUSION
Our results supported the role of D3-receptor agonism in inducing impulsivity in dopamine receptor agonists and identified a potential role of 5-HT1a receptor agonism in antipsychotics. Investigating these receptors may drive towards a better management of drug-induced impulsivity.
Topics: Humans; Dopamine Agonists; Antipsychotic Agents; Pharmacovigilance; Bayes Theorem; Disruptive, Impulse Control, and Conduct Disorders
PubMed: 36436204
DOI: 10.1111/pcn.13511 -
BMJ Case Reports Feb 2019A 47-year-old Caucasian man was referred to our clinic with a severe clinical and biochemical phenotype of endogenous hypercortisolism for further evaluation and...
A 47-year-old Caucasian man was referred to our clinic with a severe clinical and biochemical phenotype of endogenous hypercortisolism for further evaluation and treatment. In addition to confirming adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, we found left temporal hemianopsia, massively increased prolactin, increased growth hormone/insulin-like growth factor 1 values, hypogonadotropic hypogonadism and central hypothyroidism. As the cause of these abnormalities we revealed an invasive macroadenoma of the pituitary secreting ACTH, prolactin and growth hormone, resulting not only in a clinically predominant picture of Cushing's syndrome but also causing hypogonadotropic hypogonadism and central hypothyroidism. The patient responded surprisingly well to dopamine agonist treatment leading not only to normalisation of prolactin levels but also to clinical and biochemical remission of Cushing's syndrome. Tumour size decreased successively in follow-up MRI scans. Despite lacking immunohistochemical analysis of tumour tissue, we assume plurihormonal secretion of ACTH, prolactin and growth hormone from pituitary macroadenoma, which fortunately responded well to dopamine agonist treatment.
Topics: Adenoma; Adult; Dopamine Agonists; Humans; Male; Pituitary ACTH Hypersecretion; Pituitary Neoplasms; Prolactin; Treatment Outcome
PubMed: 30765454
DOI: 10.1136/bcr-2018-228045 -
Investigative Ophthalmology & Visual... Dec 2021The development of myopia in guinea pigs can be inhibited by attenuating scleral hypoxia by increasing choroidal blood perfusion (ChBP). In this study, we reduced ChBP...
PURPOSE
The development of myopia in guinea pigs can be inhibited by attenuating scleral hypoxia by increasing choroidal blood perfusion (ChBP). In this study, we reduced ChBP through surgical and pharmacological methods to determine the effect on myopia development. We also determined whether ChBP was reduced by quinpirole, a drug that enhances form-deprivation myopia (FDM).
METHODS
ChBP was reduced in the right eyes of guinea pigs via transection of the temporal ciliary arteries or daily injections of phenylephrine into the inferior peribulbar space for one week during normal ocular growth. Other guinea pigs were subjected to two weeks of monocular FDM-with facemasks, along with daily injections of quinpirole, a dopamine D2 receptor agonist, to enhance the FDM. Changes in refraction, axial length, ChBP, and choroidal thickness (ChT) were measured in both treated and fellow eyes of the treatment and control groups. Scleral hypoxia labeling with pimonidazole adducts and α-smooth muscle actin (α-SMA) protein were also measured.
RESULTS
Surgical and pharmacological reduction of ChBP induced myopia development in the treated eyes. These treatments rendered the scleral hypoxia and increased scleral α-SMA expression. Furthermore, quinpirole injections, which increased the magnitude of myopia, augmented the FDM-associated reductions in ChBP and ChT and increased the levels of scleral hypoxia and α-SMA protein.
CONCLUSIONS
Decreased ChBP in guinea pigs leads to scleral hypoxia and scleral myofibroblast transdifferentiation with increased α-SMA expression, ultimately resulting in myopia development. In future clinical trials, ChBP reduction can serve as a potential biomarker for early detection of myopia development.
Topics: Actins; Animals; Axial Length, Eye; Blood Flow Velocity; Blotting, Western; Choroid; Ciliary Arteries; Computed Tomography Angiography; Disease Models, Animal; Dopamine Agonists; Electroretinography; Guinea Pigs; Hypoxia; Muscle, Smooth; Myopia; Phenylephrine; Quinpirole; Receptors, Dopamine D2; Refraction, Ocular; Regional Blood Flow; Sclera; Tomography, Optical Coherence
PubMed: 34967855
DOI: 10.1167/iovs.62.15.30 -
Frontiers in Endocrinology 2021Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most... (Review)
Review
Pituitary neuroendocrine tumors (PitNET) are commonly benign tumors accounting for 10-25% of intracranial tumors. Prolactin-secreting adenomas represent the most predominant type of all PitNET and for this subtype of tumors, the medical therapy relies on the use of dopamine agonists (DAs). DAs yield an excellent therapeutic response in reducing tumor size and hormonal secretion targeting the dopamine receptor type 2 (D2DR) whose higher expression in prolactin-secreting adenomas compared to other PitNET is now well established. Moreover, although DAs therapy does not represent the first-line therapy for other PitNET, off-label use of DAs is considered in PitNET expressing D2DR. Nevertheless, DAs primary or secondary resistance, occurring in a subset of patients, may involve several molecular mechanisms, presently not fully elucidated. Dopamine receptors (DRs) expression is a prerequisite for a proper DA function in PitNET and several molecular events may negatively modify DR membrane expression, through the DRs down-regulation and intracellular trafficking, and DR signal transduction pathway. The current mini-review will summarise the presently known molecular events that underpin the unsuccessful therapy with DAs.
Topics: ACTH-Secreting Pituitary Adenoma; Adenoma; Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Drug Resistance, Neoplasm; Filamins; Growth Hormone-Secreting Pituitary Adenoma; Humans; Lisuride; MicroRNAs; Pergolide; Pituitary Neoplasms; Prolactinoma; Receptors, Dopamine D2; beta-Arrestins
PubMed: 35095761
DOI: 10.3389/fendo.2021.791633 -
Biomolecules Nov 2023L-DOPA is the mainstay of treatment for Parkinson's disease (PD). However, over time this drug can produce dyskinesia. A useful acute PD model for screening novel...
L-DOPA is the mainstay of treatment for Parkinson's disease (PD). However, over time this drug can produce dyskinesia. A useful acute PD model for screening novel compounds for anti-parkinsonian and L-DOPA-induced dyskinesia (LID) are dopamine-depleted dopamine-transporter KO (DDD) mice. Treatment with α-methyl--tyrosine rapidly depletes their brain stores of DA and renders them akinetic. During sensitization in the open field (OF), their locomotion declines as vertical activities increase and upon encountering a wall they stand on one leg or tail and engage in climbing behavior termed "three-paw dyskinesia". We have hypothesized that L-DOPA induces a stereotypic activation of locomotion in DDD mice, where they are unable to alter the course of their locomotion, and upon encountering walls engage in "three-paw dyskinesia" as reflected in vertical counts or beam-breaks. The purpose of our studies was to identify a valid index of LID in DDD mice that met three criteria: (a) sensitization with repeated L-DOPA administration, (b) insensitivity to a change in the test context, and (c) stimulatory or inhibitory responses to dopamine D1 receptor agonists (5 mg/kg SKF81297; 5 and 10 mg/kg MLM55-38, a novel compound) and amantadine (45 mg/kg), respectively. Responses were compared between the OF and a circular maze (CM) that did not hinder locomotion. We found vertical counts and climbing were specific for testing in the OF, while oral stereotypies were sensitized to L-DOPA in both the OF and CM and responded to D1R agonists and amantadine. Hence, in DDD mice oral stereotypies should be used as an index of LID in screening compounds for PD.
Topics: Mice; Animals; Levodopa; Dopamine Agonists; Dopamine; Dopamine Plasma Membrane Transport Proteins; Dyskinesia, Drug-Induced; Mice, Knockout; Parkinson Disease; Amantadine
PubMed: 38002340
DOI: 10.3390/biom13111658 -
European Journal of Pharmacology Aug 2022Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those...
Dopamine levels in the central nervous system change under pathological conditions such as Parkinson's disease, Huntington's disease, and addiction. Under those pathological conditions, astrocytes become reactive astrocytes characterized by morphological changes and the release of inflammatory cytokines involved in pathogenesis. However, it remains unclear whether dopamine regulates astrocytic morphology and functions. Elucidating these issues will help us to understand the pathogenesis of neurodegenerative diseases caused by abnormal dopamine signaling. In this study, we investigated the effects of dopamine on IL-6 expression and process formation in rat primary cultured astrocytes and acute hippocampal slices. Dopamine increased IL-6 expression in a concentration-dependent manner, and this was accompanied by CREB phosphorylation. The effects of a low dopamine concentration (1 μM) were inhibited by a D1-like receptor antagonist, whereas the effects of a high dopamine concentration (100 μM) were inhibited by a β-antagonist and enhanced by a D2-like receptor antagonist. Furthermore, dopamine (100 μM) promoted process formation, which was inhibited by a β-antagonist and enhanced by both an α-antagonist and a D2-like receptor antagonist. In acute hippocampal slices, both a D1-like receptor agonist and β-agonist changed astrocytic morphology. Together, these results indicate that dopamine promotes IL-6 expression and process formation via D1-like receptors and β-adrenoceptors. Furthermore, bidirectional regulation exists; namely, the effects of D1-like receptors and β-adrenoceptors were negatively regulated by D2-like receptors and α-adrenoceptors.
Topics: Animals; Astrocytes; Dopamine; Dopamine Agonists; Interleukin-6; Rats; Receptors, Adrenergic; Receptors, Adrenergic, alpha-2; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 35738452
DOI: 10.1016/j.ejphar.2022.175110 -
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 -
Pituitary Feb 2020Consensus guidelines recommend dopamine agonists (DAs) as the mainstay treatment for prolactinomas. In most patients, DAs achieve tumor shrinkage and normoprolactinemia... (Review)
Review
Consensus guidelines recommend dopamine agonists (DAs) as the mainstay treatment for prolactinomas. In most patients, DAs achieve tumor shrinkage and normoprolactinemia at well tolerated doses. However, primary or, less often, secondary resistance to DAs may be also encountered representing challenging clinical scenarios. This is particularly true for aggressive prolactinomas in which surgery and radiotherapy may not achieve tumor control. In these cases, alternative medical treatments have been considered but data on their efficacy should be interpreted within the constraints of publication bias and of lack of relevant clinical trials. The limited reports on somatostatin analogues have shown conflicting results, but cases with optimal outcomes have been documented. Data on estrogen modulators and metformin are scarce and their usefulness remains to be evaluated. In many aggressive lactotroph tumors, temozolomide has demonstrated optimal outcomes, whereas for other cytotoxic agents, tyrosine kinase inhibitors and for inhibitors of mammalian target of rapamycin (mTOR), higher quality evidence is needed. Finally, promising preliminary results from in vitro and animal reports need to be further assessed and, if appropriate, translated in human studies.
Topics: Cabergoline; Dopamine Agonists; Female; Humans; Male; Prolactinoma
PubMed: 31522358
DOI: 10.1007/s11102-019-00987-3