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Frontiers in Endocrinology 2022Prolactin is a polypeptide hormone that is well known for its role in reproductive physiology. Recent studies highlight its role in neurohormonal appetite regulation and... (Review)
Review
Prolactin is a polypeptide hormone that is well known for its role in reproductive physiology. Recent studies highlight its role in neurohormonal appetite regulation and metabolism. Elevated prolactin levels are widely associated with worsening metabolic disease, but it appears that low prolactin levels could also be metabolically unfavorable. This review discusses the pathophysiology of prolactin related metabolic changes, and the less commonly recognized effects of prolactin on adipose tissue, pancreas, liver, and small bowel. Furthermore, the effect of dopamine agonists on the metabolic profiles of patients with hyperprolactinemia are discussed as well.
Topics: Dopamine Agonists; Humans; Hyperprolactinemia; Pituitary Neoplasms; Prolactin; Prolactinoma
PubMed: 36246929
DOI: 10.3389/fendo.2022.1002320 -
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 -
Biological Psychiatry Jan 2017Schizophrenia is characterized by profound cognitive deficits that are not alleviated by currently available medications. Many of these cognitive deficits involve... (Review)
Review
Schizophrenia is characterized by profound cognitive deficits that are not alleviated by currently available medications. Many of these cognitive deficits involve dysfunction of the newly evolved, dorsolateral prefrontal cortex (dlPFC). The brains of patients with schizophrenia show evidence of dlPFC pyramidal cell dendritic atrophy, likely reductions in cortical dopamine, and possible changes in dopamine D receptors (DR). It has been appreciated for decades that optimal levels of dopamine are essential for dlPFC working memory function, with many beneficial actions arising from DR stimulation. DR are concentrated on dendritic spines in the primate dlPFC, where their stimulation produces an inverted-U dose response on dlPFC neuronal firing and cognitive performance during working memory tasks. Research in both academia and the pharmaceutical industry has led to the development of selective D agonists, e.g., the first full D agonist, dihydrexidine, which at low doses improved working memory in monkeys. Dihydrexidine has begun to be tested in patients with schizophrenia or schizotypal disorder. Initial results are encouraging, but studies are limited by the pharmacokinetics of the drug. These data, however, have spurred efforts toward the discovery and development of improved or novel new compounds, including D agonists with better pharmacokinetics, functionally selective D ligands, and DR positive allosteric modulators. One or several of these approaches should allow optimization of the beneficial effects of DR stimulation in the dlPFC that can be translated into clinical practice.
Topics: Animals; Dopamine; Dopamine Agonists; Dopamine Antagonists; Humans; Phenanthridines; Prefrontal Cortex; Receptors, Dopamine; Receptors, Dopamine D1; Receptors, Dopamine D2; Schizophrenia; Schizophrenic Psychology
PubMed: 26946382
DOI: 10.1016/j.biopsych.2015.12.028 -
The Cochrane Database of Systematic... May 2015Cocaine misuse is a disorder for which no pharmacological treatment of proven efficacy exists. Advances in neurobiology could guide future medication development. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cocaine misuse is a disorder for which no pharmacological treatment of proven efficacy exists. Advances in neurobiology could guide future medication development.
OBJECTIVES
To investigate the efficacy and acceptability of dopamine agonists alone or in combination with any psychosocial intervention for the treatment of of people who misuse cocaine.
SEARCH METHODS
We run the search on 12 January 2015. We searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE, CINAHL, PsycINFO, ICTRP, clinicaltrials.gov and screened reference lists.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) comparing dopamine agonists alone or associated with psychosocial intervention with placebo, no treatment or other pharmacological interventions.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
Twenty four studies, including 2147 participants, met the inclusion criteria. Comparing any dopamine agonist versus placebo, we found no differences for any of the outcomes considered: dropout (moderate quality of evidence), abstinence (low quality of evidence), severity of dependence (low quality of evidence), adverse events (moderate quality of evidence). This was also observed when single dopamine agonists were compared against placebo. Comparing amantadine versus antidepressants, we found low quality of evidence that antidepressants performed better for abstinence (RR 0.25, 95% CI 0.12 to 0.53) based on two studies with 44 participants. No differences were found for dropout or adverse events, for both moderate quality of evidence.The major flaws of the included studies concerned selection bias because most studies did not report information about sequence generation (80%) and allocation concealment methods (86%): half of the included studies were judged at unclear risk of performance bias and 62.5% at unclear risk of detection bias for what concerns subjective outcomes.
AUTHORS' CONCLUSIONS
Current evidence from RCTs does not support the use of dopamine agonists for treating cocaine misuse. This absence of evidence may leave to clinicians the alternative of balancing the possible benefits against the potential adverse effects of the treatment. Even the potential benefit of combining a dopamine agonist with a more potent psychosocial intervention, which was suggested by the previous Cochrane Review (Soares 2003), is not supported by the results of this Cochrane Review update.
Topics: Amantadine; Antidepressive Agents; Bromocriptine; Cocaine-Related Disorders; Depression; Dopamine Agonists; Humans; Levodopa; Randomized Controlled Trials as Topic; Selection Bias
PubMed: 26014366
DOI: 10.1002/14651858.CD003352.pub4 -
Basic & Clinical Pharmacology &... Oct 2016The currently recommended first-line treatments of erectile dysfunction (ED), phosphodiesterase type 5 inhibitors (PDE5i), for example sildenafil, are efficacious in... (Review)
Review
The currently recommended first-line treatments of erectile dysfunction (ED), phosphodiesterase type 5 inhibitors (PDE5i), for example sildenafil, are efficacious in many patients with ED of vascular origin, but this therapy is insufficient in approximately 30-40% of men with ED where there is also a neuronal affection. There is a demand of novel approaches to treat the condition. We review the possibility of modulating the dopaminergic pathways to improve erectile function. Dopamine D (D , D )- and D (D -D )-like receptors in the paraventricular area, the medial pre-optic area, the spinal cord, and in the erectile tissue are involved in erection, and several agonists developed for the treatment of Parkinson's disease are associated with increased libido. A therapeutic window for the treatment of ED was found by sublingual administration of the general dopamine receptor agonist apomorphine, but it failed mainly due to less efficacy on erectile function compared with PDE5i. To avoid the dose-limiting side effects mediated by D receptors, nausea and emesis, dopamine D receptor agonists were developed, and they induce erection in rodents, but these drugs were never introduced clinically. The β-lactamase inhibitor clavulanic acid increases dopamine and serotonin and was found to increase sexual arousal and erections, but the dose-response curve is bell-shaped. Bupropion has selectivity for inhibition of the dopamine reuptake transporter and can be used to alleviate sexual symptoms caused by other antidepressant medication, hence providing an interesting approach to treat ED. In summary, modulation of the dopaminergic pathways provides a possibility to improve the treatment of ED.
Topics: Animals; Dopamine; Dopamine Agonists; Dopaminergic Neurons; Drug Monitoring; Erectile Dysfunction; Genitalia, Male; Humans; Male; Models, Biological; Paraventricular Hypothalamic Nucleus
PubMed: 27541930
DOI: 10.1111/bcpt.12653 -
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 -
Pharmacological Research Dec 2016
Topics: Animals; Dopamine Agonists; Dopamine Antagonists; Drug Discovery; Humans; Pharmacology; Retinal Degeneration; Systems Analysis
PubMed: 27720767
DOI: 10.1016/j.phrs.2016.09.026 -
Neurobiology of Disease Oct 2023L-DOPA-induced dyskinesia (LID) remains a major complication of Parkinson's disease management for which better therapies are necessary. The contribution of the...
L-DOPA-induced dyskinesia (LID) remains a major complication of Parkinson's disease management for which better therapies are necessary. The contribution of the striatonigral direct pathway to LID is widely acknowledged but whether the striatopallidal pathway is involved remains debated. Selective optogenetic stimulation of striatonigral axon terminals induces dyskinesia in mice rendered hemiparkinsonian with the toxin 6-hydroxydopamine (6-OHDA). Here we show that optogenetically-induced dyskinesia is increased by the D2-type dopamine receptor agonist quinpirole. Although the quinpirole effect may be mediated by D2 receptor stimulation in striatopallidal neurons, alternative mechanisms may be responsible as well. To selectively modulate the striatopallidal pathway, we selectively expressed channelrhodopsin-2 (ChR2) in D2 receptor expressing neurons by crossing D2-Cre and ChR2-flox mice. The animals were rendered hemiparkinsonian and implanted with an optic fiber at the ipsilateral external globus pallidus (GPe). Stimulation of ChR2 at striatopallidal axon terminals reduced LID and also general motility during the off L-DOPA state, without modifying the pro-motor effect of low doses of L-DOPA producing mild or no dyskinesia. Overall, the present study shows that D2-type dopamine receptors and the striatopallidal pathway modulate dyskinesia and suggest that targeting striatopallidal axon terminals at the GPe may have therapeutic potential in the management of LID.
Topics: Animals; Mice; Levodopa; Quinpirole; Dopamine Agonists; Dyskinesias; Oxidopamine; Receptors, Dopamine D2
PubMed: 37683958
DOI: 10.1016/j.nbd.2023.106278 -
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 -
Free Radical Biology & Medicine Jun 2023Acute lung injury (ALI) or its severe form, acute respiratory distress syndrome (ARDS) is a life-threatening illness without effective therapeutic interventions...
Acute lung injury (ALI) or its severe form, acute respiratory distress syndrome (ARDS) is a life-threatening illness without effective therapeutic interventions currently. Multiple lines of evidence indicated that overwhelming inflammatory responses and impaired epithelial barrier contributed to the pathogenesis of ALI/ARDS. Recently, dopamine (DA) system was identified to participate in various pulmonary diseases. Here, we discovered that dopamine D1-like receptors mainly expressed in macrophages and airway epithelial cells (AECs), which were downregulated by lipopolysaccharide (LPS) challenge in ALI mouse lung. SKF38393 (SKF) is a selective agonist for D1-like receptors and was demonstrated to inhibit excessive inflammatory responses and oxidative stress in THP-1 cell-derived macrophages and Beas-2B cells, as well as improve airway epithelial barrier dysfunction induced by LPS stimulation. Moreover, SKF administration could effectively decrease pulmonary inflammation, ameliorate tissue damage in the LPS-triggered ALI mice. The broad protective actions of SKF might be attributed to the activation of Nrf2 antioxidative system by use of the specific inhibitor, ML385. This study offers evidence of potent immunoregulatory activity of SKF in macrophages, AECs as well as ALI mouse model, which opens novel therapeutic avenues for the intervention of ALI/ARDS.
Topics: Animals; Mice; Lipopolysaccharides; Dopamine Agonists; Dopamine; Acute Lung Injury; Macrophages; Epithelial Cells; Respiratory Distress Syndrome; Receptors, Dopamine D1; Lung
PubMed: 36965538
DOI: 10.1016/j.freeradbiomed.2023.03.016