Bromocriptine Monotherapy Research Articles

Bromocriptine monotherapy overcomes prostate cancer chemoresistance in preclinical models

Chemoresistance is a major obstacle in the clinical management of metastatic, castration-resistant prostate cancer (PCa). It is imperative to develop novel strategies to overcome chemoresistance and improve clinical outcomes in patients who have failed chemotherapy. Using a two-tier phenotypic screening platform, we identified bromocriptine mesylate as a potent and selective inhibitor of chemoresistant PCa cells. Bromocriptine effectively induced cell cycle arrest and activated apoptosis in chemoresistant PCa cells but not in chemoresponsive PCa cells. RNA-seq analyses revealed that bromocriptine affected a subset of genes implicated in the regulation of the cell cycle, DNA repair, and cell death. Interestingly, approximately one-third (50/157) of the differentially expressed genes affected by bromocriptine overlapped with known p53-p21- retinoblastoma protein (RB) target genes. At the protein level, bromocriptine increased the expression of dopamine D2 receptor (DRD2) and affected several classical and non-classical dopamine receptor signal pathways in chemoresistant PCa cells, including adenosine monophosphate-activated protein kinase (AMPK), p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa B (NF-κB), enhancer of zeste homolog 2 (EZH2), and survivin. As a monotherapy, bromocriptine treatment at 15 mg/kg, three times per week, via the intraperitoneal route significantly inhibited the skeletal growth of chemoresistant C4-2B-TaxR xenografts in athymic nude mice. In summary, these results provided the first preclinical evidence that bromocriptine is a selective and effective inhibitor of chemoresistant PCa. Due to its favorable clinical safety profiles, bromocriptine could be rapidly tested in PCa patients and repurposed as a novel subtype-specific treatment to overcome chemoresistance.

Neuroleptic malignant syndrome associated with bromocriptine withdrawal in Parkinson's disease — a case report

A 74-year-old man had 15-year history of Parkinson's disease and received bromocriptine monotherapy for 3 years. We present the first case report of neuroleptic malignant syndrome associated with the withdrawal of bromocriptine. The symptoms were alleviated by adequate replenishment of intravenous fluid, temperature reduction and replacement of bromocriptine. Clinicians need to be aware of this potential complication and that a thorough history of current medications is crucial to its identification.

Effectiveness of bromocriptine monotherapy or combination treatment with clomiphene for infertility in women with galactorrhea and normal prolactin: A systematic review and meta-analysis

Background: Among women with unexplained infertility, 28% to 55% of patients with galactorrhea are normoprolactinemic. Bromocriptine, a common treatment for infertile women with hyperprolactinemia, has been used in the treatment of unexplained subfertility in women with galactorrhea and normal prolactin; however, its effectiveness and safety profile have never been determined. Objective: The aim of this study was to determine the relative effectiveness and safety profile of bromocriptine monotherapy or as an adjunct to clomiphene citrate in women with galactorrhea and normal prolactin levels. Methods: We conducted a search of the Cochrane Subfertility Review Group specialized register of controlled trials (March 2010), CENTRAL (The Cochrane Library, Issue 3, 2010), MEDLINE (1950–March 2010), EMBASE (1980–March 2010), and the China Biological Medicine Database (inception to March 2010) for relevant randomized controlled trials (RCTs) using the following terms: controlled, randomized, blinded, clinical trials, humans, galactorrhea, prolactin, bromocriptine, infertility, and subfertility. Additionally, reference lists of identified articles were searched for relevant articles. Results: Of the 8 studies identified, 5 were excluded after full-text review for the following reasons: lack of a placebo group (2); difference in cointerventions (1); difference in end points (1); and systematic review (1). Therefore, 3 RCTs were included in this review. Bromocriptine administered in combination with clomiphene was found to be associated with a higher accumulative pregnancy rate compared with clomiphene monotherapy (fixed odds ratio [OR], 5.33; 95% CI, 2.62–10.88), and a lower miscarriage rate (fixed OR, 0.20; 95% CI, 0.05–0.76). Only 1 trial reported live birth as an outcome, and multiple pregnancy rates were poorly reported. Patient-reported adverse effects were mentioned in the studies, but reports were often incomplete. Conclusions: This review suggests the effectiveness of bromocriptine with clomiphene for infertility in women with galactorrhea and normal prolactin levels. Further RCTs of adequate power and of high methodologic quality are required to confirm these findings.

Long-term bromocriptine treatment of de novo patients with Parkinson's disease. A seven-year follow-up

Thirty-nine de novo patients with Parkinson's disease were treated with bromocriptine alone and followed on average for 5.9 years. Fifteen of the 39 patients did not complete the first year of observation, 12 of them because of drug intolerance. The symptomatology was tolerated well by other 24 for the first 2 years treatment. During the third year of follow-up levodopa treatment had to be instituted because of loss of response to bromocriptine. The number of fluctuations in disability was smaller in the patients whose symptomatology was controlled by bromocriptine monotherapy than in those requiring levodopa, either alone or combined with bromocriptine.

Bromocriptine versus levodopa in early Parkinson's disease.

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. 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. 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. Randomised trials evaluating the efficacy of BR monotherapy for delaying the onset of motor complications compared to LD therapy alone in PD patients. Two review authors independently evaluated the methodological quality of identified trials and extracted the data from the trials. 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. 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.

Initial bromocriptine did not change mortality in early, mild Parkinson's disease

(2001) Neurology 57, 1687. Lees AJ, Katzenschlager R, Head J, et al, on behalf of the Parkinson's Disease Research Group of the United Kingdom. . Ten-year follow-up of three different...

Bromocriptine versus levodopa in early Parkinson's disease.

Drugs that mimic dopamine as bromocriptine were introduced as monotherapy or in a 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. The present study is a systematic review of all randomized controlled trials of bromocriptine monotherapy compared with levodopa (LD) monotherapy in PD. 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 Parkinson's disease (PD). Sources including the Cochrane Library, the search strategy of the Movement Disorders Group (includes computerised searches of MEDLINE and EMBASE and hand searching of appropriate neurology journals), reference lists of the reviews found by the MEDLINE and EMBASE search-strategy, Sandoz -now Novartis- (manufacturer of BR), symposia reports, PD handbooks, contacts with colleagues who had co-ordinated trials on BR and reference lists of all included studies were used to identify randomized controlled trials (RCTs) of interest. Randomized trials were eligible for inclusion if they evaluated the efficacy of BR monotherapy for delaying the onset of motor complications compared to LD therapy in PD patients. Outcome measures that were evaluated included occurrence and severity of motor complications, changes in impairment and disability, and the occurrence of side effects. To determine the feasibility of a quantitative systematic review two independent reviewers evaluated the methodological quality of identified trials. Over the period of 1974 to January 1999 we identified six studies randomizing more than 850 patients to a BR or a LD regimen. The majority of the studies lacked sample size calculations and randomization procedure remained unclear in three trials. Only two trials were performed according to a double-blind design. Important differences between studies concerning the duration of trials, the BR titration phase, the achieved mean dose of LD or BR, and the applied outcomes were found. Because of these differences, we could not pool the data from the different trials in an attempt to perform a meta-analysis. Therefore, the available data of the individual trials was re-analysed. Subsequently, the results were interpreted against the background of the sources of heterogeneity between the studies. The occurrence of dyskinesias in three short trials was too low to allow 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 frequent 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 patients 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. This systematic review identified important sources of heterogeneity between trials. Inadequate powering of the studies and clinically relevant differences in trial duration, applied outcomes, and trial design may explain the different results and why many findings failed to reach a statistically significant level. Nevertheless, based on qualitative review of 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.

Bromocriptine monotherapy: potential in Parkinson??s disease

Bromocriptine monotherapy: potential in Parkinson??s disease

Nationwide Multicenter Prospective Study on the Long-Term Effects of Bromocriptine for Parkinson's Disease

A 10-year nationwide multicenter prospective study on the long-term efficacy of bromocriptine for Parkinson's disease is reported. Six patients remained on bromocriptine monotherapy for 10 years, while 22 patients achieved good disease control with bromocriptine plus levodopa (added during the course of the study). In the 6 patients on bromocriptine alone, the disease remained in Hoehn and Yahr stage I or II for 10 years. In the other 22 patients on bromocriptine plus levodopa therapy, disease progression was very slow for 7-8 years. None of the 6 patients remaining on bromocriptine monotherapy experienced adverse reactions like the wearing-off phenomenon, dyskinesia, or the on-off phenomenon. Among the 22 patients who started levodopa therapy during the course of the study, these adverse reactions to levodopa were infrequent (10, 3, and 3 patients, respectively). Thus, early introduction and long continuation of bromocriptine therapy with restricted concomitant use of levodopa may have led to very slow disease progression and the suppression of adverse reactions. Although the patients who could be maintained long-term on bromocriptine monotherapy might represent a population who have very slowly progressive disease, their adequate disease control and the low incidence of adverse reactions in the patients who later started concomitant levodopa suggest that the unwanted effects of levodopa may be reduced by early and sustained treatment with bromocriptine. Introduction of bromocriptine monotherapy at an early stage of Parkinson's disease or with restricted use of additional levodopa therapy to bromocriptine when necessary may be a useful strategy for achieving adequate and sustained disease control.

Seven-year follow-up study of bromocriptine therapy for Parkinson's disease.

A 7-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Of 22 patients who had been on bromocriptine monotherapy for 7 years (group B), 16 remained improved or remained in the same stages of Hoehn and Yahr, and no wearing-off phenomenon or dyskinesia was observed. In another 56 patients who were started on bromocriptine alone, but in whom combination therapy with levodopa was instituted at some time in the 7 years (group BL), disease progressed faster than in group B. A wearing-off phenomenon and dyskinesia occurred in 34% and 5.4% of the patients, respectively. These manifestations appeared only after initiation of levodopa. The favorable course of group B suggests possible neuroprotective effects of bromocriptine or may be due to the inevitable selection of patients who had a favorable course originally.

Drug therapy of Parkinson's disease. An overview.

The nation-wide collaborative study on the bromocriptine monotherapy and bromocriptine-levodopa combination therapy was completed in November 1990, and the results were reported during the symposium on the Long-Term Treatment of Parkinson's Disease held in Tokyo in October 1991. The author briefly reviewed the history of treatment of Parkinson's disease, and current and future trends in its drug therapy as an introductory remark. The personal view on the principle of drug treatment for parkinsonian patients is the judicious concomitant use of several different classes of anti-parkinsonian drugs, including levodopa, dopamine agonists, monoamine oxidase inhibitors, anticholinergics, and amantadine HCl utilizing the smallest effective dose for each drug. The treatment of Parkinson's disease seems to be moving slowly from mere symptomatic therapy to the one which is aiming the protection of nigral cells. Recent progress in this field is also briefly reviewed.

A Nationwide Collaborative Study on the Long-Term Effects of Bromocriptine in Patients with Parkinson’s Disease

The interim results of the nationwide collaborative study on the long-term effects of bromocriptine in patients with Parkinson's disease are reported. Four years ago, two prospective clinical studies were started to evaluate the long-term effects of bromocriptine in Parkinson's disease. The first was to investigate the long-term effects of bromocriptine monotherapy and the second to see the long-term effects of a combination therapy of bromocriptine with levodopa. Patients who had never been treated with levodopa were placed on bromocriptine monotherapy, and those who had been treated with levodopa for not more than 5 years were allocated randomly to either the combination or the levodopa group. Two hundred and eighty-six patients were enrolled in the former study and 416 in the latter. Among the 286 patients, 164 continued for further observation at the end of the fourth year, and 74 of them were still being treated with bromocriptine monotherapy. However, in 78, levodopa had to be added. Among the 416 patients in the second study, 216 were allocated to the combination group and 200 to the levodopa control group. At the end of the fourth year, 130 in the former and 140 in the latter group remained for further observation. In all three groups, a gradual loss of efficacy was noted. The rate of efficacy loss appeared largest in the monotherapy group and smallest in the combination group. Effects on tremor and rigidity are still maintained, but effects on akinesia and gait were lost by the end of the fourth year in all groups. Wearing-off and dyskinesias seem to be better managed by the combination therapy. The incidence of wearing-off was very small in the monotherapy group. No serious side effects were encountered except for 1 patient who died of pulmonary fibrosis in the combination group.

Third Interim Report of the Nationwide Collaborative Study on the Long-Term Effects of Bromocriptine in the Treatment of Parkinsonian Patients

The interim results obtained up to the end of the 3rd year of the multicenter nationwide cooperative study on the long-term effects of bromocriptine in parkinsonian patients are reported. Bromocriptine monotherapy could be continued in approximately 33% of the patients at the mean maintenance dose of 11.4 mg/day. The combined use of bromocriptine (11.1 mg/day) in parkinsonian patients already treated with levodopa had a favorable influence on the long-term side effects of levodopa such as the on-off phenomenon and dyskinesia. The beneficial effects of bromocriptine, levodopa and an early combination on parkinsonian symptoms such as rigidity and tremor remained at the end of the 3rd year. However, the effects of each mode of therapy on another parkinsonian symptom, akinesia, ceased by the end of the 3rd year.

Second Interim Report of the Nation-Wide Collaborative Study on the Long-Term Effects of Bromocriptine in the Treatment of Parkinsonian Patients

The interim data obtained up to the end of the 2nd year of the nation-wide multicentric cooperative study on the long-term effects of bromocriptine in parkinsonian patients revealed the following results. Firstly, the bromocriptine monotherapy could be continued in about 40% of the patients at the mean maintenance dose of 10.8 mg daily. Secondly, the additional use of bromocriptine in parkinsonian patients already treated with levodopa had a favorable influence on late side effects of levodopa such as on-off phenomenon and dyskinesia. No significant difference has been found so far as to the management of the wearing-off phenomenon between the patients with levodopa alone and those with levodopa and bromocriptine.