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Journal of Neurotrauma Jan 2021Dopamine D1 and D2 receptors differ with respect to patterns of regional brain distribution and behavioral effects. Pre-clinical work suggests that D1 agonists enhance...
Dopamine D1 and D2 receptors differ with respect to patterns of regional brain distribution and behavioral effects. Pre-clinical work suggests that D1 agonists enhance working memory, but the absence of selective D1 agonists has constrained using this approach in humans. This study examines working memory performance in mild traumatic brain injury (mTBI) patients when given pergolide, a mixed D1/D2 agonist, compared with bromocriptine, a selective D2 agonist. Fifteen individuals were studied 1 month after mTBI and compared with 17 healthy controls. At separate visits, participants were administered 1.25 mg bromocriptine or 0.05 mg pergolide prior to functional magnetic resonance imaging (MRI) using a working memory task (visual-verbal n-back). Results indicated a significant group-by-drug interaction for mean performance across n-back task conditions, where the mTBI group showed better performance on pergolide relative to bromocriptine, whereas controls showed the opposite pattern. There was also a significant effect of diagnosis, where mTBI patients performed worse than controls, particularly while on bromocriptine, as shown in our prior work. Functional MRI activation during the most challenging task condition (3-back > 0-back contrast) showed a significant group-by-drug interaction, with the mTBI group showing increased activation relative to controls in working memory circuitry while on pergolide, including in the left inferior frontal gyrus. Across participants there was a positive correlation between change in activation in this region and change in performance between drug conditions. Results suggest that activation of the D1 receptor may improve working memory performance after mTBI. This has implications for the development of pharmacological strategies to treat cognitive deficits after mTBI.
Topics: Adolescent; Adult; Brain; Brain Concussion; Bromocriptine; Dopamine Agonists; Female; Humans; Magnetic Resonance Imaging; Male; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Pergolide; Young Adult
PubMed: 32635808
DOI: 10.1089/neu.2020.7087 -
Molecular Metabolism Sep 2021The therapeutic effects of the dopamine D2 receptor (D2R) agonist, bromocriptine, in type 2 diabetes (T2D) have been attributed to central nervous system actions....
Dopamine D2 receptor agonist, bromocriptine, remodels adipose tissue dopaminergic signalling and upregulates catabolic pathways, improving metabolic profile in type 2 diabetes.
BACKGROUND AND OBJECTIVES
The therapeutic effects of the dopamine D2 receptor (D2R) agonist, bromocriptine, in type 2 diabetes (T2D) have been attributed to central nervous system actions. However, peripheral dopamine directly modulates glucose uptake in insulin-sensitive tissues and lipid metabolism in adipose tissue (AT). We hypothesized that the dopaminergic system may be impaired in the adipose tissue of patients with T2D and that the therapeutic actions of bromocriptine could involve the modulation of metabolism in this tissue.
METHODS
The expression of dopamine receptors was evaluated in visceral AT samples from patients with obesity and stratified in several groups: insulin sensitive (IS); insulin resistance (IR) normoglycaemic; insulin resistant prediabetic; insulin resistant diabetic, according to Ox-HOMA2IR, fasting glycaemia and HbA1c levels. T2D Goto-Kakizaki rats (GK) were fed a high-caloric diet (HCD) for five months and treated with bromocriptine (10 mg/kg/day, i.p.) in the last month. The levels of dopaminergic system mediators and markers of insulin sensitivity and glucose and lipid metabolism were assessed in the peri-epididymal adipose tissue (pEWAT) and brown (BAT) adipose tissues, liver, and skeletal muscle.
RESULTS
Patients with IR presented a decreasing trend of DRD1 expression in the visceral adipose tissue, being correlated with the expression of UCP1, PPARA, and insulin receptor (INSR) independently of insulin resistance and body mass index. Although no differences were observed in DRD2, DRD4 expression was significantly decreased in patients with prediabetes and T2D. In HCD-fed diabetic rats, bromocriptine increased D1R and tyrosine hydroxylase (TH) levels in pEWAT and the liver. Besides reducing adiposity, bromocriptine restored GLUT4 and PPARγ levels in pEWAT, as well as postprandial InsR activation and postabsorptive activation of lipid oxidation pathways. A reduction of liver fat, GLUT2 levels and postprandial InsR and AMPK activation in the liver was observed. Increased insulin sensitivity and GLUT4 levels in BAT and an improvement of the overall metabolic status were observed.
CONCLUSIONS
Bromocriptine treatment remodels adipose tissue and the liver dopaminergic system, with increased D1R and TH levels, resulting in higher insulin sensitivity and catabolic function. Such effects may be involved in bromocriptine therapeutic effects, given the impaired expression of dopamine receptors in the visceral adipose tissue of IR patients, as well as the correlation of D1R expression with InsR and metabolic mediators.
Topics: Adult; Aged; Animals; Bariatric Surgery; Bromocriptine; Cohort Studies; Diabetes Mellitus, Type 2; Disease Models, Animal; Dopamine; Dopamine Agonists; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Lipid Metabolism; Male; Metabolic Networks and Pathways; Metabolome; Metabolomics; Middle Aged; Obesity; Rats; Receptors, Dopamine D2
PubMed: 33933677
DOI: 10.1016/j.molmet.2021.101241 -
NeuroImage Jun 2017The dedifferentiation theory of aging proposes that a reduction in the specificity of neural representations causes declines in complex cognition as people get older,... (Randomized Controlled Trial)
Randomized Controlled Trial
The dedifferentiation theory of aging proposes that a reduction in the specificity of neural representations causes declines in complex cognition as people get older, and may reflect a reduction in dopaminergic signaling. The present pharmacological fMRI study investigated episodic memory-related dedifferentiation in young and older adults, and its relation to dopaminergic function, using a randomized placebo-controlled double-blind crossover design with the agonist Bromocriptine (1.25mg) and the antagonist Sulpiride (400mg). We used multi-voxel pattern analysis to measure memory specificity: the degree to which distributed patterns of activity distinguishing two different task contexts during an encoding phase are reinstated during memory retrieval. As predicted, memory specificity was reduced in older adults in prefrontal cortex and in hippocampus, consistent with an impact of neural dedifferentiation on episodic memory representations. There was also a linear age-dependent dopaminergic modulation of memory specificity in hippocampus reflecting a relative boost to memory specificity on Bromocriptine in older adults whose memory was poorer at baseline, and a relative boost on Sulpiride in older better performers, compared to the young. This differed from generalized effects of both agents on task specificity in the encoding phase. The results demonstrate a link between aging, dopaminergic function and dedifferentiation in the hippocampus.
Topics: Adult; Aged; Aging; Brain; Brain Mapping; Bromocriptine; Carrier Proteins; Dopamine; Dopamine Agonists; Dopamine Antagonists; Female; Humans; Male; Memory, Episodic; Middle Aged; Models, Neurological; Sulpiride; Young Adult
PubMed: 25800211
DOI: 10.1016/j.neuroimage.2015.03.031 -
Postgraduate Medical Journal Sep 1986
Clinical Trial
Topics: Bromocriptine; Clinical Trials as Topic; Dopamine; Glaucoma; Humans; Intraocular Pressure
PubMed: 3543911
DOI: 10.1136/pgmj.62.731.819 -
The Cochrane Database of Systematic... 2001Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening... (Review)
Review
BACKGROUND
Long term levodopa therapy in Parkinson's disease is associated with the development of motor complications including abnormal involuntary movements and a shortening response to each dose (wearing off phenomenon). It is thought that dopamine agonists can reduce the duration of immobile off periods and the need for levodopa therapy whilst maintaining or improving motor impairments and only minimally increasing dopaminergic adverse events.
OBJECTIVES
To compare the efficacy and safety of adjuvant cabergoline therapy versus bromocriptine in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.
SEARCH STRATEGY
Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn Limited.
SELECTION CRITERIA
Randomised controlled trials of cabergoline versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, off time measurements and the frequency of withdrawals and adverse events.
MAIN RESULTS
Cabergoline has been compared with bromocriptine in five randomised, double-blind, parallel group studies including 1071 patients. Only one of the phase II studies was medium term (36 weeks), the others all being short term (12 -15 weeks). The non-significant difference in off time reduction produced by cabergoline compared with bromocriptine was 0.29 hours/day in favour of the former (weighted mean difference; 95% CI -0.10, 0.68; p = 0.15). Dyskinesia reported as an adverse event was significantly increased with cabergoline compared with bromocriptine (Peto odds ratio 1.57; 95% CI 1.05, 2.35; p = 0.03). Motor impairment and disability were measured in four of the studies using the UPDRS rating scale but the small differences in UPDRS ADL (part II) and motor (part III) scores were not statistically significant in any study. Similarly, no significant difference in Schwab and England score was seen. The number of patients rated as much or very much improved on a clinician's global impression scale was similar with both agonists. Levodopa dose reduction was no different between cabergoline and bromocriptine. There was more confusion with cabergoline (Peto odds ratio 2.02; 95% CI 1.09, 3.76; p = 0.03). Otherwise, dopaminergic adverse events were comparable with these agonists and no significant difference in all cause withdrawal rate was found.
REVIEWER'S CONCLUSIONS
Cabergoline produces similar benefits to bromocriptine in off time reduction, motor impairment and disability ratings, and levodopa dose reduction over the first three months of therapy. Dyskinesia and confusion were increased with cabergoline but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two agonists.
Topics: Antiparkinson Agents; Bromocriptine; Cabergoline; Dopamine Agonists; Dyskinesia, Drug-Induced; Ergolines; Humans; Levodopa; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 11279721
DOI: 10.1002/14651858.CD001519 -
The Cochrane Database of Systematic... 2000To compare the efficacy and safety of adjuvant pramipexole versus bromocriptine therapy in patients with Parkinson's disease, already established on levodopa and... (Review)
Review
OBJECTIVES
To compare the efficacy and safety of adjuvant pramipexole versus bromocriptine therapy in patients with Parkinson's disease, already established on levodopa and suffering from motor complications.
SEARCH STRATEGY
Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn and Boehringer Ingelheim.
SELECTION CRITERIA
Randomised controlled trials of pramipexole versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of drop outs and adverse events.
MAIN RESULTS
One randomised controlled trial has compared pramipexole with bromocriptine using a double-blind, parallel group, multicentre design. It was not powered to examine differences between active treatment arms. There was a larger reduction in off time with pramipexole therapy compared with bromocriptine (weighted mean difference 1.4 hours; 0, 2.8, 95% CI). No differences occurred in dyskinesia rating scale, dyskinesia as an adverse event or UPDRS complication score. The UPDRS ADL and motor scores showed similar improvements compared to placebo with both agonists. Levodopa dose reduction was similar with both agonists. Subscales of the Functional Status Questionnaire showed significant improvements compared to placebo with both agonists. The finding that the EuroQol improved significantly compared with placebo with pramipexole but not bromocriptine should be treated with caution. Dopaminergic adverse events were similar with each agonist, as was the all cause withdrawal rate.
REVIEWER'S CONCLUSIONS
Although pramipexole and bromocriptine improved off time and reduced parkinsonian motor impairments and disability compared with placebo, no conclusions regarding their comparative effectiveness and safety can be drawn as this single trial did not have adequate power to assess such differences. Further larger trials are required to examine this issue in the future.
Topics: Antiparkinson Agents; Benzothiazoles; Bromocriptine; Dopamine Agonists; Drug Tolerance; Humans; Levodopa; Parkinson Disease; Pramipexole; Randomized Controlled Trials as Topic; Thiazoles
PubMed: 10908539
DOI: 10.1002/14651858.CD002259 -
Iranian Biomedical Journal Jan 2020In recent years, nanotechnology with modern advances in the macromolecular design of nano-carriers has proved to be helpful in the development of drugs delivery systems....
BACKGROUND
In recent years, nanotechnology with modern advances in the macromolecular design of nano-carriers has proved to be helpful in the development of drugs delivery systems. This research represents a novel co-administration of nano-vehicles, known as liposomes. Liposomes efficiently encapsulate curcumin and bromocriptine (BR) in a polymer structure, which results in enhanced aqueous solubility of the mentioned hydrophobic agents and higher bioavailability of the drugs.
METHODS
Preparation of curcumin and BR liposomes were carried out by the thin film method, and the amounts of purified drug and its release were analyzed. After dose determination, the human lung cancer cells (QU-DB) were exposed to BR and curcumin liposomes for 12, 24, and 48 h. Then the viability and apoptosis assays were carried out by using tetrazolium dye and flow cytometry technique, respectively.
RESULTS
In this research, in vitro anti-cancer effects of former nano-formulations on lung cancer cells was confirmed, and no cytotoxicity effects of these nano-preparations were observed in the normal cells (HFLF-PI5).
DISCUSSION
Our findings suggest the nano-liposomal drugs as effective anti-cancer agents; however, additional clinical examinations are required.
Topics: Apoptosis; Bromocriptine; Cell Line, Tumor; Cell Survival; Curcumin; Drug Delivery Systems; Drug Liberation; Humans; Liposomes; Lung Neoplasms; Nanoparticles; Particle Size
PubMed: 31454860
DOI: 10.29252/ibj.24.1.24 -
The Cochrane Database of Systematic... Oct 2007Drugs that mimic dopamine as bromocriptine were introduced as monotherapy or in combination with LD in the hope that this approach would prevent or delay the onset of... (Review)
Review
BACKGROUND
Drugs that mimic dopamine as bromocriptine were introduced as monotherapy or in combination with LD in the hope that this approach would prevent or delay the onset of motor complications in patients with Parkinson's disease (PD). However, hitherto, the role of bromocriptine (BR) in this issue has remained controversial.
OBJECTIVES
To assess the efficacy and safety of bromocriptine (BR) monotherapy for delaying the onset of motor complications associated with levodopa (LD) therapy in patients with PD.
SEARCH STRATEGY
We searched the Movement Disorders Group trials register which includes MEDLINE and EMBASE; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); handsearched appropriate neurology journals and reference lists of reviews found by the search-strategy. We also contacted Sandoz -now Novartis- (manufacturer of BR) and contacted colleagues who had co-ordinated trials on BR.
SELECTION CRITERIA
Randomised trials evaluating the efficacy of BR monotherapy for delaying the onset of motor complications compared to LD therapy alone in PD patients.
DATA COLLECTION AND ANALYSIS
Two review authors independently evaluated the methodological quality of identified trials and extracted the data from the trials.
MAIN RESULTS
Six trials with 850 participants were included. The trials were of low methodological quality and were heterogeneous so we were unable to perform a meta-analysis. The occurrence of dyskinesias in three short trials was too low to draw any conclusion. The results of the longer trials indicate a lower occurrence of dyskinesias in the BR tier. In five trials that evaluated dystonia, this motor complication occurred less frequently in the BR tier. However, for both dyskinesias and dystonia a statistically significant difference in favour of BR emerged only in the largest trial. There was a trend for wearing-off and on-off fluctuations to occur less frequently in the BR group. Although all trials evaluated participants at the impairment level, only the largest trial reported a significantly larger improvement for the LD tier during the first year of therapy. Concerning disability, which was evaluated by five trials no statistically significant differences were found. Overall, a statistically larger number of dropouts occurred in the BR group because of an inadequate therapeutic response or intolerable side effects.
AUTHORS' CONCLUSIONS
Based on a qualitative review of the available data we conclude that in the treatment of early Parkinson's disease, bromocriptine may be beneficial in delaying motor complications and dyskinesias with comparable effects on impairment and disability in those patients that tolerate the drug.
Topics: Antiparkinson Agents; Bromocriptine; Humans; Levodopa; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 17943771
DOI: 10.1002/14651858.CD002258.pub2 -
Pharmacology, Biochemistry, and Behavior Jun 2024Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
BACKGROUND
Pituitary lactotrophs are under tonic dopaminergic inhibitory control and bromocriptine treatment blocks prolactin secretion.
METHODS
Sleep and local field potential were addressed for 72 h after bromocriptine treatments applied during the different stages of the estrus cycle and for 24 h in the early- and middle postpartum period characterized by spontaneously different dynamics of prolactin release in female rats.
RESULTS
Sleep changes showed strong dependency on the estrus cycle phase of the drug application. Strongest increase of wakefulness and reduction of slow wave sleep- and rapid eye movements sleep appeared during diestrus-proestrus and middle postpartum treatments. Stronger sleep-wake effects appeared in the dark phase in case of the estrus cycle treatments, but in the light phase in postpartum treatments. Slow wave sleep and REM sleep loss in case of estrus cycle treatments was not compensated at all and sleep loss seen in the first day post-injection was gained further later. In opposition, slow wave sleep loss in the light phase after bromocriptine injections showed compensation in the postpartum period treatments. Bromocriptine treatments resulted in a depression of local field potential delta power during slow wave sleep while an enhancement in beta and gamma power during wakefulness regardless of the treatment timing.
CONCLUSIONS
These results can be explained by the interplay of dopamine D2 receptor agonism, lack of prolactin release and the spontaneous homeostatic sleep drive being altered in the different stages of the estrus cycle and the postpartum period.
Topics: Animals; Bromocriptine; Female; Postpartum Period; Rats; Receptors, Dopamine D2; Dopamine Agonists; Estrous Cycle; Rats, Wistar; Sleep; Wakefulness; Prolactin
PubMed: 38537873
DOI: 10.1016/j.pbb.2024.173754 -
Fertility and Sterility Mar 1988Thirty-two patients with ovarian hyperstimulation were randomized to receive bromocriptine or placebo from cycle day 5 onward. Bromocriptine decreased serum and... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Thirty-two patients with ovarian hyperstimulation were randomized to receive bromocriptine or placebo from cycle day 5 onward. Bromocriptine decreased serum and follicular fluid prolactin (PRL), accelerated ovarian follicle growth, increased serum and follicular fluid estradiol, lowered luteal phase progesterone, and shortened the luteal phase length of the cycle. The maximal luteal phase estradiol and progesterone concentrations correlated with each other in the placebo group, but not in the bromocriptine group. These findings indicate that hypoprolactinemia interferes with ovarian function. The unchanged concentrations of gonadotropic hormones and pattern of luteinizing hormone pulsation during bromocriptine suggest direct ovarian effects of hypoprolactinemia. Because PRL suppression enhanced follicular responses and inhibited corpus luteum formation and function, the follicular and corpus luteum actions of PRL may be different.
Topics: Adult; Bromocriptine; Female; Humans; Menstrual Cycle; Ovarian Follicle; Ovary; Prolactin
PubMed: 3342895
DOI: No ID Found