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The Cochrane Database of Systematic... Apr 2021Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation in assisted reproduction technology (ART). It is characterised by enlarged ovaries and an acute fluid shift from the intravascular space to the third space, resulting in bloating, increased risk of venous thromboembolism, and decreased organ perfusion. Most cases are mild, but forms of moderate or severe OHSS appear in 3% to 8% of in vitro fertilisation (IVF) cycles. Dopamine agonists were introduced as a secondary prevention intervention for OHSS in women at high risk of OHSS undergoing ART treatment. OBJECTIVES: To assess the effectiveness and safety of dopamine agonists in preventing OHSS in women at high risk of developing OHSS when undergoing ART treatment.
SEARCH METHODS
We searched the following databases from inception to 4 May 2020: Cochrane Gynaecology and Fertility Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and PsycINFO for randomised controlled trials (RCTs) assessing the effect of dopamine agonists on OHSS rates. We also handsearched reference lists and grey literature.
SELECTION CRITERIA
We considered RCTs for inclusion that compared dopamine agonists with placebo/no intervention or another intervention for preventing OHSS in ART. Primary outcome measures were incidence of moderate or severe OHSS and live birth rate. Secondary outcomes were rates of clinical pregnancy, multiple pregnancy, miscarriage, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles, abstracts, and full texts of publications; selected studies; extracted data; and assessed risk of bias. We resolved disagreements by consensus. We reported pooled results as odds ratios (OR) and 95% confidence interval (CI) by the Mantel-Haenszel method. We applied GRADE criteria to judge overall quality of the evidence.
MAIN RESULTS
The search identified six new RCTs, resulting in 22 included RCTs involving 3171 women at high risk of OHSS for this updated review. The dopamine agonists were cabergoline, quinagolide, and bromocriptine. Dopamine agonists versus placebo or no intervention Dopamine agonists probably lowered the risk of moderate or severe OHSS compared to placebo/no intervention (OR 0.32, 95% CI 0.23 to 0.44; 10 studies, 1202 participants; moderate-quality evidence). This suggests that if the risk of moderate or severe OHSS following placebo/no intervention is assumed to be 27%, the risk following dopamine agonists would be between 8% and 14%. We are uncertain of the effect of dopamine agonists on rates of live birth (OR 0.96, 95% CI 0.60 to 1.55; 3 studies, 362 participants; low-quality evidence). We are also uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy, miscarriage or adverse events (very low to low-quality evidence). Dopamine agonists plus co-intervention versus co-intervention Dopamine agonist plus co-intervention (hydroxyethyl starch, human albumin, or withholding ovarian stimulation 'coasting') may decrease the risk of moderate or severe OHSS compared to co-intervention (OR 0.48, 95% CI 0.28 to 0.84; 4 studies, 748 participants; low-quality evidence). Dopamine agonists may improve rates of live birth (OR 1.21, 95% CI 0.81 to 1.80; 2 studies, 400 participants; low-quality evidence). Dopamine agonists may improve rates of clinical pregnancy and miscarriage, but we are uncertain if they improve rates of multiple pregnancy or adverse events (very low to low-quality evidence). Dopamine agonists versus other active interventions We are uncertain if cabergoline improves the risk of moderate or severe OHSS compared to human albumin (OR 0.21, 95% CI 0.12 to 0.38; 3 studies, 296 participants; very low-quality evidence), prednisolone (OR 0.27, 95% CI 0.05 to 1.33; 1 study; 150 participants; very low-quality evidence), hydroxyethyl starch (OR 2.69, 95% CI 0.48 to 15.10; 1 study, 61 participants; very low-quality evidence), coasting (OR 0.42, 95% CI 0.18 to 0.95; 3 studies, 320 participants; very low-quality evidence), calcium infusion (OR 1.83, 95% CI 0.88 to 3.81; I² = 81%; 2 studies, 400 participants; very low-quality evidence), or diosmin (OR 2.85, 95% CI 1.35 to 6.00; 1 study, 200 participants; very low-quality evidence). We are uncertain of the effect of dopamine agonists on rates of live birth (OR 1.08, 95% CI 0.73 to 1.59; 2 studies, 430 participants; low-quality evidence). We are uncertain of the effect of dopamine agonists on clinical pregnancy, multiple pregnancy or miscarriage (low to moderate-quality evidence). There were no adverse events reported.
AUTHORS' CONCLUSIONS
Dopamine agonists probably reduce the incidence of moderate or severe OHSS compared to placebo/no intervention, while we are uncertain of the effect on adverse events and pregnancy outcomes (live birth, clinical pregnancy, miscarriage). Dopamine agonists plus co-intervention may decrease moderate or severe OHSS rates compared to co-intervention only, but we are uncertain whether dopamine agonists affect pregnancy outcomes. When compared to other active interventions, we are uncertain of the effects of dopamine agonists on moderate or severe OHSS and pregnancy outcomes.
Topics: Abortion, Spontaneous; Administration, Oral; Aminoquinolines; Bromocriptine; Cabergoline; Dopamine Agonists; Ergolines; Female; Fertilization in Vitro; Humans; Live Birth; Ovarian Hyperstimulation Syndrome; Placebos; Pregnancy; Pregnancy Rate; Randomized Controlled Trials as Topic; Sperm Injections, Intracytoplasmic
PubMed: 33851429
DOI: 10.1002/14651858.CD008605.pub4 -
Tremor and Other Hyperkinetic Movements... 2021Apomorphine is a potent dopamine agonist used in the treatment of advanced and fluctuating Parkinson's Disease. However the need for its subcutaneous infusion can lead...
BACKGROUND
Apomorphine is a potent dopamine agonist used in the treatment of advanced and fluctuating Parkinson's Disease. However the need for its subcutaneous infusion can lead to skin reactions.
PHENOMENOLOGY SHOWN
We illustrate necrotic ulcers at infusion sites as a rare event during continuous subcutaneous apomorphine infusion.
EDUCATIONAL VALUE
This case demonstrates the rare adverse event of necrotic ulcers in a patient with long term apomorphine infusion.
Topics: Antiparkinson Agents; Apomorphine; Dopamine Agonists; Humans; Injections, Subcutaneous; Ulcer
PubMed: 35070491
DOI: 10.5334/tohm.648 -
British Journal of Pharmacology Feb 2015Rotigotine acts as a dopamine receptor agonist with high affinity for the dopamine D2, D3, D4 and D5 receptors but with a low affinity for the dopamine D1 receptor. We...
BACKGROUND AND PURPOSE
Rotigotine acts as a dopamine receptor agonist with high affinity for the dopamine D2, D3, D4 and D5 receptors but with a low affinity for the dopamine D1 receptor. We have investigated this further in radioligand binding and functional studies and compared the profile of rotigotine with that of other drugs used in the treatment of Parkinson's disease (PD).
EXPERIMENTAL APPROACH
The binding of rotigotine to human dopamine D1, D2, D3, D4 and D5 receptors was determined in radioligand binding studies using [(3)H]rotigotine and compared with that of standard antagonist radioligands. Functional interactions of rotigotine with human dopamine receptors was also determined.
KEY RESULTS
[(3)H]rotigotine can be used as an agonist radioligand to label all dopamine receptor subtypes and this can be important to derive agonist affinity estimates. Rotigotine maintains this high affinity in functional studies at all dopamine receptors especially D1, D2 and D3 receptors and, to a lesser extent, D4 and D5 receptors. Rotigotine, like apomorphine but unlike ropinirole and pramipexole, was a potent agonist at all dopamine receptors.
CONCLUSIONS AND IMPLICATIONS
Rotigotine is a high-potency agonist at human dopamine D1, D2 and D3 receptors with a lower potency at D4 and D5 receptors. These studies differentiate rotigotine from conventional dopamine D2 agonists, used in the treatment of PD, such as ropinirole and pramipexole which lack activity at the D1 and D5 receptors, but resembles that of apomorphine which has greater efficacy in PD than other dopamine agonists but has suboptimal pharmacokinetic properties.
Topics: Cell Line; Dopamine Agonists; Humans; Radioligand Assay; Receptors, Dopamine; Tetrahydronaphthalenes; Thiophenes
PubMed: 25339241
DOI: 10.1111/bph.12988 -
Journal of Medicinal Chemistry May 2020To identify novel D dopamine receptor (D3R) agonists, we conducted a high-throughput screen using a β-arrestin recruitment assay. Counterscreening of the hit compounds...
To identify novel D dopamine receptor (D3R) agonists, we conducted a high-throughput screen using a β-arrestin recruitment assay. Counterscreening of the hit compounds provided an assessment of their selectivity, efficacy, and potency. The most promising scaffold was optimized through medicinal chemistry resulting in enhanced potency and selectivity. The optimized compound, ML417 (), potently promotes D3R-mediated β-arrestin translocation, G protein activation, and ERK1/2 phosphorylation (pERK) while lacking activity at other dopamine receptors. Screening of ML417 against multiple G protein-coupled receptors revealed exceptional global selectivity. Molecular modeling suggests that ML417 interacts with the D3R in a unique manner, possibly explaining its remarkable selectivity. ML417 was also found to protect against neurodegeneration of dopaminergic neurons derived from iPSCs. Together with promising pharmacokinetics and toxicology profiles, these results suggest that ML417 is a novel and uniquely selective D3R agonist that may serve as both a research tool and a therapeutic lead for the treatment of neuropsychiatric disorders.
Topics: Animals; CHO Cells; Cricetulus; Dopamine Agonists; Dose-Response Relationship, Drug; Drug Discovery; HEK293 Cells; Hep G2 Cells; Humans; Induced Pluripotent Stem Cells; Male; Mice; Mice, Inbred C57BL; Protein Structure, Secondary; Receptors, Dopamine D3
PubMed: 32342685
DOI: 10.1021/acs.jmedchem.0c00424 -
Neuropharmacology Oct 2023Many patients with Parkinson's disease (PD) experiencing l-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID...
Many patients with Parkinson's disease (PD) experiencing l-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID is unknown. We set out to compare temporal and topographic profiles of abnormal involuntary movements (AIMs) after l-DOPA dose challenges including or not the dopamine agonist ropinirole. Twenty-five patients with PD and a history of dyskinesias were sequentially administered either l-DOPA alone (150% of usual morning dose) or an equipotent combination of l-DOPA and ropinirole in random order. Involuntary movements were assessed by two blinded raters prior and every 30 min after drug dosing using the Clinical Dyskinesia Rating Scale (CDRS). A sensor-recording smartphone was secured to the patients' abdomen during the test sessions. The two raters' CDRS scores were highly reliable and concordant with models of hyperkinesia presence and severity trained on accelerometer data. The dyskinesia time curves differed between treatments as the l-DOPA-ropinirole combination resulted in lower peak severity but longer duration of the AIMs compared with l-DOPA alone. At the peak of the AIMs curve (60-120 min), l-DOPA induced a significantly higher total hyperkinesia score, whereas in the end phase (240-270 min), both hyperkinesia and dystonia tended to be more severe after the l-DOPA-ropinirole combination (though reaching statistical significance only for the item, arm dystonia). Our results pave the way for the introduction of a combined l-DOPA-ropinirole challenge test in the early clinical evaluation of antidyskinetic treatments. Furthermore, we propose a machine-learning method to predict CDRS hyperkinesia severity using accelerometer data.
Topics: Humans; Antiparkinson Agents; Dopamine Agonists; Dyskinesia, Drug-Induced; Dystonia; Hyperkinesis; Levodopa; Oxidopamine; Parkinson Disease
PubMed: 37315840
DOI: 10.1016/j.neuropharm.2023.109630 -
Psychopharmacology Jan 20182-Bromoterguride, a dopamine D receptor partial agonist with antagonist properties at serotonin 5-HT receptors and α-adrenoceptors, meets the prerequisites of a...
RATIONALE
2-Bromoterguride, a dopamine D receptor partial agonist with antagonist properties at serotonin 5-HT receptors and α-adrenoceptors, meets the prerequisites of a putative atypical antipsychotic drug (APD). We recently showed that 2-bromoterguride is effective in tests of positive symptoms of schizophrenia in rats without inducing extrapyramidal side effects or metabolic changes.
OBJECTIVE
In continuation of our recent work, we now investigated the effect of 2-bromoterguride on apomorphine and phencyclidine (PCP)-induced disruptions of prepulse inhibition (PPI) of the acoustic startle response, a measure of sensory gating. In addition, we used subchronic PCP treatment to produce cognitive deficits and social aversion, and assessed the effect of 2-bromoterguride on the performance in the novel object recognition (NOR) task (model for studying cognitive deficit symptoms of schizophrenia) and the social interaction test (model for studying negative symptoms of schizophrenia). Finally, we extended the side effect profile of 2-bromoterguride by measuring the prolactin response to systemic administration of the drug in rats.
RESULTS
Treatment with 2-bromoterguride (0.1 and 0.3 mg/kg) reversed PPI deficits induced by apomorphine and PCP, respectively. Subchronic PCP induced impairments in object memory and social interaction behavior which were ameliorated by 2-bromoterguride but not by clozapine and aripiprazole, respectively. Prolactin concentration in blood serum was not elevated at 1, 2, or 4 h post-2-bromoterguride treatment, which further supports the safe and effective use of this drug.
CONCLUSIONS
Our data support 2-bromoterguride as a promising APD candidate due to its beneficial effect on cognitive impairments and negative symptoms of schizophrenia.
Topics: Animals; Antipsychotic Agents; Apomorphine; Cognition Disorders; Dopamine Agonists; Lisuride; Male; Memory Disorders; Phencyclidine; Prolactin; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D2; Recognition, Psychology; Reflex, Startle; Schizophrenic Psychology; Social Behavior
PubMed: 28971230
DOI: 10.1007/s00213-017-4747-x -
The American Journal of Managed Care Oct 2001The etiologic enigma of systemic lupus erythematosus (SLE) has so far precluded a fully integrated approach to understanding and managing the disease. As new findings... (Review)
Review
The etiologic enigma of systemic lupus erythematosus (SLE) has so far precluded a fully integrated approach to understanding and managing the disease. As new findings continue to uncover relationships between the endocrine system and the besieged immune system in lupus patients, however, researchers have an opportunity to rethink the direction of their investigative efforts. A successful approach to development of long-awaited new treatments may well include modulation of specific hormones. The peptide hormone prolactin may be associated with SLE disease activity. The dopamine agonist bromocriptine, which inhibits pituitary secretion of prolactin, has been shown in a variety of small animal and human trials to reduce disease activity in SLE. Continued research may show that it can be an attractive alternative or adjacent therapy in cases where hydroxychloroquine is contraindicated.
Topics: Animals; Bromocriptine; Dopamine Agonists; Estrogens; Hormones; Humans; Lupus Erythematosus, Systemic; Prolactin; Testosterone
PubMed: 11680780
DOI: No ID Found -
Brain Stimulation Oct 2012Dopamine agonist therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are antiparkinsonian treatments that act on a different part of the basal...
BACKGROUND
Dopamine agonist therapy and deep brain stimulation (DBS) of the subthalamic nucleus (STN) are antiparkinsonian treatments that act on a different part of the basal ganglia-thalamocortical motor circuitry, yet produce similar symptomatic improvements.
OBJECTIVE/HYPOTHESIS
The purpose of this study was to identify common and unique brain network features of these standard treatments.
METHODS
We analyzed images produced by H(2)(15)O positron emission tomography (PET) of patients with Parkinson's disease (PD) at rest. Nine patients were scanned before and after injection of apomorphine, and 11 patients were scanned while bilateral stimulators were off and while they were on.
RESULTS
Both treatments produced common deactivations of the neocortical sensorimotor areas, including the supplementary motor area, precentral gyrus, and postcentral gyrus, and in subcortical structures, including the putamen and cerebellum. We observed concomitant activations of the superior parietal lobule and the midbrain in the region of the substantia nigra/STN. We also detected unique, treatment-specific changes with possible motor-related consequences in the basal ganglia, thalamus, neocortical sensorimotor cortex, and posterolateral cerebellum. Unique changes in nonmotor regions may reflect treatment-specific effects on verbal fluency and limbic functions.
CONCLUSIONS
Many of the common effects of these treatments are consistent with the standard pathophysiologic model of PD. However, the common effects in the cerebellum are not readily explained by the model. Consistent deactivation of the cerebellum is interesting in light of recent reports of synaptic pathways directly connecting the cerebellum and basal ganglia, and may warrant further consideration for incorporation into the model.
Topics: Adult; Aged; Antiparkinson Agents; Apomorphine; Brain; Brain Mapping; Deep Brain Stimulation; Dopamine Agonists; Female; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Parkinson Disease; Radionuclide Imaging; Treatment Outcome
PubMed: 22019080
DOI: 10.1016/j.brs.2011.09.002 -
Aging Jun 2021Dopamine receptor, a polypeptide chain composed of 7 hydrophobic transmembrane regions, is a new and vital drug target, especially Dopamine receptor 2(D2). Targeting...
Dopamine receptor, a polypeptide chain composed of 7 hydrophobic transmembrane regions, is a new and vital drug target, especially Dopamine receptor 2(D2). Targeting dopamine receptors, Dopamine receptor agonists are a class of drugs similar in function and structure to dopamine and can directly act on dopamine receptors and activate it. Clinically, Dopamine receptor agonist drugs have achieved significant therapeutic effects on prolactinoma and Parkinson's Disease. In the study, we virtually screened a series of potential effective agonists of Dopamine receptor by computer techniques. Firstly, we used the Molecular Docking (LibDock) step to screen out some molecules that can dock well with the protein. Then, analysis of toxicity prediction and ADME (adsorption, distribution, metabolism and excretion) were carried out. More precise molecular docking (CDOCKER) and 3-Dimensional Quantitative Structure-Activity Relationship Modeling Study(3D-QSAR) pharmacophore generation were implemented to research and explore these compounds' binding mechanism with Dopamine receptor. Last but not least, to assess compound's binding stabilities, we carried out a molecular dynamic analysis. As the results show, two compounds (ZINC000008860530 and ZINC000004096987) from the small molecule database (ZINC database) were potential effective agonists of Dopamine receptor. These two compounds can combine with Dopamine receptor with higher affinity and proved to be no toxic. The cell experiment showed that two compounds could inhibit the proliferation and PRL secretion of MMQ cells (pituitary tumor cells). Thus, this study provided valuable information about Dopamine receptor agonist-based drug discovery. So, this study will benefit patients with prolactinoma and Parkinson's disease a lot.
Topics: Biological Products; Bromocriptine; Cell Line, Tumor; Cell Survival; Dopamine Agonists; Drug Evaluation, Preclinical; Humans; Hydrogen Bonding; Ligands; Molecular Docking Simulation; Molecular Dynamics Simulation; Prolactin; Receptors, Dopamine
PubMed: 34170848
DOI: 10.18632/aging.203180 -
Epilepsia Sep 2021Dopamine type 2 receptor (D2R) agonists have anticonvulsant effect, whereas D2R antagonists increase seizure risk, but the mechanism of this action has not been...
Dopamine type 2 receptor (D2R) agonists have anticonvulsant effect, whereas D2R antagonists increase seizure risk, but the mechanism of this action has not been delineated. We tested whether D2R agonists activate parvalbumin (PV)-containing inhibitory interneurons to suppress seizures. We treated frontal lobe onset seizures with a D2R agonist sumanirole, and it suppressed seizures. We used activity reporter TRAP2 mice and found that injection of D2R agonist led to extensive activation of PV interneurons in the cortex and striatum ipsilateral to the seizure focus. D2R agonists activate PV interneurons, which in turn inhibit principal neurons, potentially explaining their anticonvulsant effect.
Topics: Animals; Anticonvulsants; Dopamine; Dopamine Agonists; Interneurons; Mice; Parvalbumins; Seizures
PubMed: 34331457
DOI: 10.1111/epi.17004