Bromocriptine

The physico-chemical properties and in vivo efficacies of two nanoparticulate systems delivering the antiparkinsonian drug bromocriptine (BC) were compared in the present study. Monoolein Aqueous Dispersions (MADs) and Nanostructured Lipid Carriers (NLCs) were produced and characterized. Cryogenic transmission electron microscopy (cryo-TEM) and X-ray diffraction revealed the morphology of MAD and NLC. Dimensional distribution was determined by Photon Correlation Spectroscopy (PCS) and Sedimentation Field Flow Fractionation (SdFFF). In particular, BC was shown to be encapsulated with high entrapment efficiency both in MAD and in NLC, according to SdFFF combined with HPLC. Two behavioral tests specific for akinesia (bar test) or akinesia/bradykinesia (drag test) were used to compare the effects of the different BC formulations on motor disabilities in 6-hydroxydopamine hemilesioned rats in vivo, a model of Parkinson's disease. Both free BC and BC-NLC reduced the immobility time in the bar test and enhanced the number of steps in the drag test, although the effects of encapsulated BC were longer lasting (5 h). Conversely, BC-MAD was ineffective in the bar test and improved stepping activity in the drag test to a much lower degree than those achieved with the other preparations. We conclude that MAD and NLC can encapsulate BC, although only NLC provide long-lasting therapeutic effects possibly extending BC half-life in vivo.

Some treatments used for Parkinson's disease attenuate locomotor depression in rats treated with reserpine and a-methyl-p-tyrosine. In the present study memantine (2.5, 5.0mg/kg), amantadine (10, 20mg/kg) (both uncompetitive NMDA antagonists), and L-deprenyl (1.0, 5.0 mg/kg; MAO-B inhibitor) were tested for possible synergistic interactions with the dopamine agonists: bromocriptine (2.5, 5.0mg/kg) and L-DOPA (50, 100mg/kg, + benserazide, 100mg/kg). At higher doses, memantine (10mg/kg), amantadine (40mg/kg), bromocriptine (5 and 10mg/kg) and L-DOPA (100, 200mg/kg) but not Ldeprenyl (up to 10 mg/kg) produced a pronounced increase in locomotor activity when given alone. The combination of memantine, amantadine and L-deprenyl with bromocriptine did not result in synergism of action and, at best, an additive effect was seen. On the other hand the combination of these agents with L-DOPA produced a pronounced synergistic effect. Hence, the clinical observation that coadministration of L-DOPA with either memantine or amantadine results in enhancement of their action is also reflected in an animal model of Parkinson's disease. Such a combination therapy should allow the use of lower doses of both drugs which may reduce the occurrence of side effects and may also be predicted to have additional benefits related to the neuroprotective properties of memantine, amantadine, and L-deprenyl.

Background.Type 2 diabetes (T2DM) patients, including those in good glycemic control, have an increased risk of cardiovascular disease (CVD). Maintaining good glycemic control may reduce long-term CVD risk. However, other risk factors such as elevated vascular sympathetic tone and/or endothelial dysfunction may be stronger potentiators of CVD. This study evaluated the impact of bromocriptine-QR, a sympatholytic dopamine D2 receptor agonist, on progression of metabolic disease and CVD in T2DM subjects in good glycemic control (HbA1c ≤7.0%).Methods.1834 subjects (1219 bromocriptine-QR; 615 placebo) with baseline HbA1c ≤7.0% derived from the Cycloset Safety Trial (this trial is registered with ClinicalTrials.gov Identifier:NCT00377676), a 12-month, randomized, multicenter, placebo-controlled, double-blind study in T2DM, were evaluated. Treatment impact upon a prespecified composite CVD endpoint (first myocardial infarction, stroke, coronary revascularization, or hospitalization for ang...

Good results have been reported with combined use of octreotide and bromocriptine in acromegalic Caucasians. Data concerning the efficacy and tolerability of this combination treatment in Chinese acromegalic patients are scanty. The aim of this study was to assess the efficacy and tolerability of combined therapy using bromocriptine and octreotide in the treatment of acromegaly in Chinese patients and to compare the cost-effectiveness of various regimes. Sixteen Chinese acromegalic patients with growth hormone (GH) concentration not suppressible to below 5 mU/L (2 microg/L) during an extended OGTT were recruited to undergo four phases of the study. During the study period, the patients were given bromocriptine alone, bromocriptine and low dose octreotide, bromocriptine and medium dose octreotide, and medium dose octreotide alone. Plasma concentrations of GH and insulin-like growth factor-1 (IGF-1) were measured before and after the completion of each phase. The number of patients re...

Cabergoline is a new long-acting dopamine agonist that is very effective and well tolerated in patients with pathological hyperprolactinemia. The aim of this study was to examine, in a very large number of hyperprolactinemic patients, the ability to normalize PRL levels with cabergoline, to determine the effective dose and tolerance, and to assess the effect on clinical symptoms, tumor shrinkage, and visual field abnormalities. We also evaluated the effects of cabergoline in a large subgroup of patients with bromocriptine intolerance or -resistance. We retrospectively reviewed the files of 455 patients (102 males and 353 females) with pathological hyperprolactinemia treated with cabergoline in 9 Belgian centers. Among these patients, 41% had a microadenoma; 42%, a macroadenoma; 16%, idiopathic hyperprolactinemia; and 1%, an empty sella. The median pretreatment serum PRL level was 124 μg/L (range, 16–26,250 μg/L). A subgroup of 292 patients had previously been treated with bromocript...

Breastfeeding is widely acknowledged to have important health benefits for infants and mothers. Milk thistle (Silybum marianum fruits) has been recently proposed to be used by nursing mothers for stimulating milk production; however, the mode of action of this herbal drug is still unknown. In this paper, we have evaluated the effect of a micronized standardized extract of S. marianum (Silymarin BIO-C s ¼ Piùlatte s ) on the serum levels of prolactin in female rats. A 14-day treatment with Silymarin BIO-C s (25-200 mg/kg, given orally) increased, in a dose dependent manner, the serum prolactin levels. Moreover, after a 66-day discontinuation of Silymarin BIO-C s treatment, prolactin levels were still significantly elevated although we observed a trend to decrease that was counteracted by a further 7-day treatment with Silymarin BIO-C s . Bromocriptine, a dopamine D 2 receptor agonist, (1-10 mg/kg, os) significantly and in a dose dependent manner, reduced the serum prolactin levels; bromocriptine, at the dose of 1 mg/ kg, significantly reduced the high serum prolactin levels induced by Silymarin BIO-C s . In conclusion, we have shown that an extract from S. marianum fruits significantly increases circulating prolactin levels in female rats; this effect seems to involve, at least in part, dopamine D 2 receptors.

Maternal hypoprolactinemia at the end of lactation in rats reduces milk production and is associated with offspring's malnutrition. Since malnutrition during development is also known to have long lasting effects on cognition and emotion, in the present study we tested the hypothesis that maternal hypoprolactinemia, induced by bromocriptine treatment, at the end of the lactating period affects memory/learning, noveltyseeking and anxiety-like behaviors in adult male Wistar rats using, respectively, the radial arm water maze (RAWM), the hole board (HB) arena and the elevated plus-maze (EPM). We also analyzed serum corticosterone and thyroid hormone levels at postnatal day (PN) 21. Lactating dams were treated with bromocriptine (BRO, 1 mg twice a day, inhibiting prolactin) or saline from PN19 to 21 (the last 3 days of lactation). BRO offspring had hypercorticosteronemia and hypothyroidism at PN21. In the RAWM, reductions in latency observed in CON rats were initially more accentuated than in BRO ones. By the end of the testing period, latencies became similar between groups. No difference was observed between groups regarding the number of nose-pokes in the HB. In the EPM, BRO rats stayed less time in and had fewer entries into the openarms than CON ones. This pattern of results indicates that maternal bromocriptine treatment at the end of the lactating period results in poorer memory/learning performance and in higher levels of anxiety-like behavior in the adult offspring, demonstrating that even a relatively short period of malnutrition during development can have long lasting detrimental effects regarding cognition and emotion.

Background-The dopamine (DA) D 2 receptor (D2R) agonist bromocriptine (BC) decreases body fat in animal and human models and increases lean muscle mass, improves glucose intolerance and insulin resistance, and reduces triglycerides and free fatty acids. We have previously shown a negative correlation between D2R and body weight in obese individuals and in rodents, and that chronic food restriction increases D2R binding in genetically obese rats. The purpose of this study was to assess whether the antiobesity and metabolic effects of BC are related to changes in midbrain DA and D2R activity by measuring D2R and DA transporter (DAT) binding in a genetic (leptin-receptor-deficient) and environmental (diet-induced) rodent obesity model.

Prolactin-secreting adenomas (prolactinomas) account for approximately 30% of pituitary adenomas and 50 to 60% of functional pituitary tumors. They are the most common type of functioning pituitary tumor and are second in frequency to nonfunctioning adenomas in overall incidence. One published estimate of their prevalence is 100 cases per 1 million persons; 21 however, based on the results of a recent metaanalysis of the literature, one may infer that this may be a gross underdiagnosis. According to this metaanalysis, MR imaging and histological examinations demonstrate that approximately 17% of patients harbor a microadenoma; one third of these tumors stain positive for prolactin, which indicates the potential for secretion in a large number of incidental adenomas (W. T. Couldwell, unpublished observations). Prolactinomas commonly cause reproductive and sexual dysfunction; macroadenomas can cause local mass effect, resulting in visual compromise, cavernous sinus compression, and hypopituitarism. The objectives for treatment of hyperprolactinemia due to prolactinomas are to normalize the hyperprolactinemic state, preserve residual pituitary function, reduce tumor mass, and prevent disease recurrence.

Several agents have been utilised for therapy of mastalgia based on data from small trials. No meta-analysis of trials on mastalgia exists. We have conducted a meta-analysis on trials on mastalgia published in the English language. Study was restricted to randomised controlled trials comparing Bromocriptine, Danazol, Evening primrose oil (EPO) and Tamoxifen with placebo. The analysis was carried out on the REVMAN statistical package. Weighted mean difference in the pain score in favour of Bromocriptine was À16.31(95% CI À26.35 to À6.27). Danazol produced a significant benefit with a mean pain score difference À20.23(95% CI À28.12 to À12.34). EPO did not offer any advantage over placebo in pain relief, mean pain score difference being À2.78 (95% CI À7.97 to 2.40). Tamoxifen achieved a relative risk (RR) of pain relief of 1.92 (95% CI 1.42-2.58). Tamoxifen is associated with least side effects and should be the drug of first choice.

The interaction between rat and human liver cytochromes P450 with a series of lysergic acid derivatives and ergopeptide alkaloids was studied by difference visible spectroscopy. Ergopeptides, like bromocriptine, ergocryptine and dihydroergotamine, strongly interacted with rat liver microsomes with the appearance of a difference spectrum which is characteristic of their binding to a protein site close to the heme. The intensity of this spectrum was clearly dependent on the amounts of P450s 3A in the microsomes and was at its maximum in dexamethasone-treated rat microsomes. All the ergopeptides studied exhibited a high affinity for rat P450s 3A (K-around 1 pM), although lysergic acid derivatives not bearing the tripeptide moiety failed to give significant interactions with these P450s. A cyclic azatripeptide exhibiting a structure very similar to that of the tripeptide moiety of ergopeptides also interacted with P450s 3A with appearance of an intense type I difference spectrum. Very similar results were observed with two allelic forms of human liver P450 3A4, P450 NF25 and P450 hPCN1, produced in yeast. In both cases all the ergopeptides studied showed high affinities for the P450s (K? 0.6-2.2 pM) and an intense shift from the low-spin to the high-spin state upon substrate binding (60-100% spin shift). Lysergic acid derivatives not bearing the tripeptide group of ergopeptides also completely failed to interact with P450s 3A4.

One hundred and twenty nine de novo patients with idiopathic Parkinson's disease are being followed over a 5 year period in a double-blind multicentre study comparing low-dose bromocriptine (< 30 mg/day) with low-dose levodopa-carbidopa (< 600/150 mg/day). Sixty six patients have been randomised to bromocriptine and 63 patients to levodopa-carbidopa. Improvement has been greater in the levodopa-carbidopa group than in the bromocriptine group. Involuntary movements have so far only occurred in patients on levodopa-carbidopa, the incidence being much lower than is usually described with conventional doses. Mild, end-of-dose failure has occurred in both treatment groups; however, no patient has developed the "on-off' phenomenon. Low-dose levodopa-carbidopa appears to be a more effective anti-Parkinsonian treatment than lowdose bromocriptine but more prone to cause dyskinesia.

Rationale Pharmacological stimulation of D2 receptors modulates prefrontal neural activity associated with working memory (WM) processing. The T allele of a functional single-nucleotide polymorphism (SNP) within DRD2 (rs1076560 G > T) predicts reduced relative expression of the D2S receptor isoform and less efficient neural cortical responses during WM tasks. Objective We used functional MRI to test the hypothesis that DRD2 rs1076560 genotype interacts with pharmacological stimulation of D2 receptors with bromocriptine on prefrontal responses during different loads of a spatial WM task (N-Back). Methods Fifty-three healthy subjects (38 GG and 15 GT) underwent two 3-T functional MRI scans while performing the 1-, 2-and 3-Back versions of the N-Back WM task. Before the imaging sessions, either bromocriptine or placebo was administered to all subjects in a counterbalanced order. A factorial repeated-measures ANOVA within SPM8 (p<0.05, family-wise error corrected) was used. Results On bromocriptine, GG subjects had reduced prefrontal activity at 3-Back together with a significant decrement in performance, compared with placebo. On the other hand, GT subjects had lower activity for the same level of performance at 1-Back but a trend for reduced behavioral performance in the face of unchanged activity at 2-Back. Conclusions These results indicate that bromocriptine stimulation modulates prefrontal activity in terms of disengagement or of efficiency depending on DRD2 genotype and working memory load.

Current research on seabirds suggests a key role of hormones in the trade-off between self-maintenance and parental investment through their influence on foraging decisions during the breeding period. Although prolactin is known to have major effects on parental care, its role in foraging behavior has rarely been investigated in seabirds to date. The aim of this study was to assess the influence of an experimental decrease in prolactin levels on foraging decisions and its consequences on breeding success in free-living seabirds. To achieve this, we implanted bromocriptine (an inhibitor of prolactin secretion) in male Adélie penguins (Pygoscelis adeliae), monitored their foraging behavior using time-depth recorders over several trips, and recorded their reproductive output. On average 8 ± 0.5 days after implantation, we showed that bromocriptine administration led to an efficient decrease in prolactin levels. However, no differences were seen in foraging trip durations between bromocriptineimplanted birds and controls. Moreover, the time spent diving and the number of dives performed per trip were similar in both groups. By contrast, all diving parameters (including diving efficiency) were negatively affected by the treatment during the first at-sea trip following the treatment. Finally, the treatment did not affect adult body condition or chick growth and survival. Our study highlights the short-term negative effect of low prolactin levels on diving effort, but indicates that a short-term and/or low-magnitude decrease in prolactin levels alone is not sufficient to modify consistently the body maintenance or the parental investment of Adélie penguins.

Dopamine is known as the main neurotransmitter modulating the activation of the reward system of the brain. The DRD2 TaqIA polymorphism is associated with dopamine D2 receptor density which plays an important role in the context of reward. Persons carrying an A1 allele have a lower D2 receptor density and a higher risk to show substance abuse. The present study

Seasonal changes in adaptations associated with winter coping strategies have been frequently studied. Central among the suite of energy-saving, winter-coping strategies is the suspension of reproductive activities. The inhibition of reproduction by nontropical rodents is mediated by daylength changes. Although balanced annual energy budgets are critical, survival and subsequent reproductive success also require avoiding predators, illness, and early death. Because the stressors of winter could lead to suppressed immune function, we hypothesized that animals should have evolved survival strategies involving immunoenhancement. Short daylengths provide a predictive cue to individuals that could be used to enhance immune function in advance of stress-induced immunosuppression. In Experiment 1, adult female deer mice (Peromyscus maniculatus) were housed in either long (LD 16:8) or short (LD 8:16) days for 8 weeks, then injected with the chemical carcinogen 9,10-dimethyl-1,2benzanthracene (DMBA) dissolved in dimethyl sulfoxide (DMSO) or with the DMSO vehicle alone. Animals were evaluated weekly for 8 weeks after injection. None of the animals treated with DMSO developed tumors in any of the experiments. Nearly 90% of the long-day deer mice injected with DMBA developed squamous cell carcinoma. None of the short-day deer mice injected with DMBA developed tumors. Small lesions developed at the site of injection; short-day females had less severe lesions and healed faster than long-day females. Immunoglobulin G (IgG) response to i.p. injection of sheep red blood cells (SRBC) did not differ between photoperiodic conditions. The role of estrogens in the photoperiodic responses was evaluated in Experiment 2: Ovariectomized or sham-ovariectomized deer mice received estradiol benzoate replacement therapy or a control procedure in long daylengths for 8 weeks prior to injection of DMBA or DMSO, then were monitored for 8 additional weeks. Females treated with DMBA developed tumors at the same rate, regardless of estrogen manipulation. Estrogen did not affect healing rates. In Experiment 3, female deer mice were injected with a slurry of microspheres that either contained bromocriptine or were empty. Suppression of prolactin with bromocryptine resulted in a decrease of tumor incidence from 55.6% to 24% in long-day females 8 weeks after injection with DMBA. Healing rates were not affected by prolactin manipulations. Silastic capsules that were filled with either melatonin or cholesterol were implanted into long-day female deer mice in Experiment 4; 8 weeks later, females received an injection of either DMBA or DMSO, then were monitored for 8 weeks. Approximately 66% of females implanted with cholesterol and injected with DMSO developed histologically verified tumors. None of the melatonin-implanted mice developed tumors. Melatonin did not affect healing rates. Taken together, these results indicate that photoperiod can exert a functionally significant effect on immune processes and clinical disease.

A 19-year-old female sustained 8 per cent full thickness petrol flame burns to the neck, chest, breasts, upper abdomen and portions of the right upper limb. The patient had been breast-feeding until the time of the injury. Following assessment of the risks of potential complications such as engorgement, hyperprolactinaemia, mastitis, milk fistulae, glandular loss, scarring and nipple distortion, surgical tangential excision was delayed until bromocriptine produced cessation of lactation and breast involution occurred. This case report demonstrates that consideration of the potential problems in burns to the lactating breasts and prophylactic management can lead to successful healing and probable restoration of function.

Breastfeeding is widely acknowledged to have important health benefits for infants and mothers. Milk thistle (Silybum marianum fruits) has been recently proposed to be used by nursing mothers for stimulating milk production; however, the mode of action of this herbal drug is still unknown. In this paper, we have evaluated the effect of a micronized standardized extract of S. marianum (Silymarin BIO-C s ¼ Piùlatte s ) on the serum levels of prolactin in female rats. A 14-day treatment with Silymarin BIO-C s (25-200 mg/kg, given orally) increased, in a dose dependent manner, the serum prolactin levels. Moreover, after a 66-day discontinuation of Silymarin BIO-C s treatment, prolactin levels were still significantly elevated although we observed a trend to decrease that was counteracted by a further 7-day treatment with Silymarin BIO-C s . Bromocriptine, a dopamine D 2 receptor agonist, (1-10 mg/kg, os) significantly and in a dose dependent manner, reduced the serum prolactin levels; bromocriptine, at the dose of 1 mg/ kg, significantly reduced the high serum prolactin levels induced by Silymarin BIO-C s . In conclusion, we have shown that an extract from S. marianum fruits significantly increases circulating prolactin levels in female rats; this effect seems to involve, at least in part, dopamine D 2 receptors.

Background: Neuroleptic malignant syndrome (NMS) represents an iatrogenic form of malignant catatonia, and simple catatonia has been shown to predispose to NMS. Objective: The authors present the case of a bipolar patient with catatonic features who developed NMS after receiving haloperidol. Method: Supportive therapy, including rehydration, electrolyte restoration, and blood pressure aids were given, together with antipyretics, antibiotics, and anticoagulants. The patient was also started on bromocriptine and diazepam. Results: Supportive care, diazepam, and dopamine agonists yielded only partial benefit. However, switching from diazepam to lorazepam, in combination with electroconvulsive therapy (ECT) and a long-acting dopamine agonist led to the resolution of NMS. Conclusion: This case sheds further light on the relationship between catatonia and NMS. As noted in the literature, ECT in combination with lorazepam proved to be safe and effective for NMS.

Ever since, the concept of catatonia has been the focus of debate, a major point of discussion being its nosological status. The question rises whether it is to be considered a syndrome with a wide variety of causes and clinical signs or a distinct clinical entity. Since catatonia shares a number of symptoms with the neuroleptic malignant syndrome (NMS) and similar treatments can be used in both conditions, it has also been suggested that NMS and catatonia are two variants of the same disorder. In this article we describe five cases of catatonia and NMS in order to approach this nosological question. The clinical similarity between both syndromes is demonstrated in our cases. On the level of pathophysiology however, catatonia and NMS are quite different, with catatonia rather being a cortical psychomotor syndrome and NMS a subcortical motor disorder. Similarities can be explained by means of well-known models of basal ganglia function. The nosological problem, however, can only be resolved when the concept of catatonia is better defined.

This paper is the final chapter of the long-running UK Parkinson's Disease Research Group (PDRG) trial, which randomised 782 patients with early Parkinson's disease (PD) between 1985 and 1990 to one of three treatment arms: levo-dopa (LD) alone, selegiline plus LD, or bromocriptine alone. The primary outcome measures were mortality and motor disability, and for this final assessment, mini mental state examination (MMSE) and a quality of life analysis (Short Form-36) were included. In 1995, a statistically higher death rate in the selegiline plus LD versus the LD alone arms was reported, 1 leading to the termination of this arm of the trial. This final follow-up paper analysed the follow-up of all patients at a median of 11.4 years.

Pituitary carcinomas are extremely rare. In general, the initial clinical, biochemical, and histological characteristics are of minimal utility in distinguishing benign adenomas from pituitary carcinomas. We describe a 63-year-old woman with a macroprolactinoma, who presented with diplopia and blurred vision. This unusual initial presentation and the subsequent aggressive clinical course, with diffuse local and distant intramedulary metastases, prompted us in retrospect to make a detailed analysis of the therapeutic interventions and histology. In addition, we reviewed all available literature on published cases of malignant prolactinoma and detailed their epidemiological, clinical, and histopathological characteristics. In brief, it is postulated that pituitary carcinomas arise from the transformation of initially large, but benign, adenomas. Unusual and/or atypical clinical manifestations appear to occur more frequently. In vivo, the development of dopamine agonist resistance in invasive macroprolactinoma is indicative of malignancy and should prompt the clinician to perform a biopsy of the tumor. For pituitary tumors that exhibit high mitotic activity, increased Ki-67 and/or p53 immunoreactivity, it may be useful to denote these tumors as 'atypical' prolactinomas to raise the possibility of future malignant development.

The objective of this study is to update a previous evidence-based medicine (EBM) review on Parkinson's disease (PD) treatments, adding January 2001 to January 2004 information. The Movement Disorder Society (MDS) Task Force prepared an EBM review of PD treatments covering data up to January 2001. The authors reviewed Level I (randomized clinical trials) reports of pharmacological and surgical interventions for PD, published as full articles in English (January 2001-January 2004). Inclusion criteria and ranking followed the original program and adhered to EBM methodology. For Efficacy Conclusions, treatments were designated Efficacious, Likely Efficacious, Non-Efficacious, or Insufficient Data. Four clinical indications were considered for each intervention: prevention of disease progression; treatment of Parkinsonism, as monotherapy and as adjuncts to levodopa where indicated; prevention of motor complications; treatment of motor complications. Twenty-seven new studies qualified for efficacy review, and others covered new safety issues. Apomorphine, piribedil, unilateral pallidotomy, and subthalamic nucleus stimulation moved upward in efficacy ratings. Rasagiline, was newly rated as Efficacious monotherapy for control of Parkinsonism. New Level I data moved human fetal nigral transplants, as performed to date, from Insufficient Data to Nonefficacious for the treatment of Parkinsonism, motor fluctuations, and dyskinesias. Selegiline was reassigned as Non-efficacious for the prevention of dyskinesias. Other designations did not change. In a field as active in clinical trials as PD, frequent updating of therapy-based reviews is essential. We consider a 3-year period a reasonable time frame for published updates and are working to establish a Web-based mechanism to update the report in an ongoing manner.

We have performed a 14-month, prospective, randomized, double-blind, placebo-controlled study to evaluate the effect of deprenyl and levodopa/carbidopa (Sinemet) on the progression of signs and symptoms in patients with mild Parkinson's disease (PD). One hundred one untreated PD patients were randomly assigned to one of the following four treatment groups: Group I, deprenyl + Sinemet; Group 11, placebo-deprenyl + Sinemet; Group 111, deprenyl + bromocriptine; and Group IV, placebo-deprenyl + bromocriptine. The final visit was performed at 14 months, i.e., 2 months after withdrawal of deprenyl or its placebo and 7 days after withdrawal of Sinemet or bromocriptine. Deterioration in Unified Parkinson's Disease Rating Score (UPDRS) between untreated baseline and final visits was used as an index of disease progression. Placebo-treated patients deteriorated by 5.8 2 1.4 points, while deprenyl-treated patients deteriorated by . This effect was sufficiently powerful that a significant deprenyl effect could be detected in the subgroup of 41 patients randomized to Sinemet ( p < 0.01) as well as in the 23 patients who completed a 14-day washout of Sinemet or bromocriptine ( p < 0.05). No difference in the extent of deterioration was detected in patients randomized to Sinemet versus bromocriptine. This study demonstrates that deprenyl attenuates deterioration in UPDRS score in patients with early PD. These findings are not readily explained by the drug's symptomatic effects and are consistent with the hypothesis that deprenyl has a neuroprotective effect.

Prolactinomas, the most common pituitary adenomas, are important causes of infertility. Bromocriptine remains the treatment of choice for managing hyperprolactinemia in most of these cases. Breastfeeding in mothers receiving bromocriptine is often doubtful and matter of concern for most people. Here we report a case, where by timely intervention and skilled counseling, exclusive breastfeeding could be established in a mother receiving bromocriptine for the treatment of hyperprolactinemia. [Indian J Pediatr 2006; 73 (5) : 435-436]

The Harderian glands in Syrian hamsters exhibit a striking sexual dimorphism. Male Harderian glands show two cell types and low levels of porphyrins and melatonin. Of the enzymes involved in the synthesis of melatonin, N-acetyltransferase (NAT) and hydroxyindole-0methyltransferase (HIOMT) show high and low activity levels, respectively. Female Harderian glands show but one cell type and have high porphyrin and melatonin levels, low NAT activity, and high HIOMT activity. In castrated males, the Harderian glands exhibit a female pattern of morphology, porphyrin levels, and indoleamine metabolism. In an attempt to determine whether prolactin is involved in this sexually dimorphic response of the Harderian glands, intact and castrated male and intact female hamsters were injected daily with 500 pg of bromocriptine, a dopamine agonist. Bromocriptine led to reduced serum prolactin levels in all groups. It had no apparent effect on the Harderian glands of intact males. In contrast, in castrated males bromocriptine prevented the postcastrational rise in porphyrin levels but had no effect on NAT or HIOMT activities. In females, bromocriptine treatment had no effect on porphyrin concentrations or HIOMT activity; it led to a statistically significant increase in NAT activity. We propose that testosterone inhibits Harderian porphyrin synthesis while dopamine or prolactin stimulates it.

In these reviews we discuss the management of endocrine disorders, with the exception of diabetes mellitus, as they occur in pregnancy. Although taking account of the literature, so far as it is possible we give our own opinions as to optimal management and, where appropriate, provide illustrative case reports. Part I deals with disorders of the thyroid and parathyroid glands, Part II with disorders of the pituitary, adrenals and ovaries.

The physico-chemical properties and in vivo efficacies of two nanoparticulate systems delivering the antiparkinsonian drug bromocriptine (BC) were compared in the present study. Monoolein Aqueous Dispersions (MADs) and Nanostructured Lipid Carriers (NLCs) were produced and characterized. Cryogenic transmission electron microscopy (cryo-TEM) and X-ray diffraction revealed the morphology of MAD and NLC. Dimensional distribution was determined by Photon Correlation Spectroscopy (PCS) and Sedimentation Field Flow Fractionation (SdFFF). In particular, BC was shown to be encapsulated with high entrapment efficiency both in MAD and in NLC, according to SdFFF combined with HPLC. Two behavioral tests specific for akinesia (bar test) or akinesia/bradykinesia (drag test) were used to compare the effects of the different BC formulations on motor disabilities in 6-hydroxydopamine hemilesioned rats in vivo, a model of Parkinson's disease. Both free BC and BC-NLC reduced the immobility time in the bar test and enhanced the number of steps in the drag test, although the effects of encapsulated BC were longer lasting (5 h). Conversely, BC-MAD was ineffective in the bar test and improved stepping activity in the drag test to a much lower degree than those achieved with the other preparations. We conclude that MAD and NLC can encapsulate BC, although only NLC provide long-lasting therapeutic effects possibly extending BC half-life in vivo.

Rose MF, Rose SR. Melatonin accelerates metamorphosis in Xenopus luevis. J. Pineal Res. 1998; 24:90-95. 0 Munksgaard, Copenhagen Abstract: Delayed metamorphosis associated with large body size has been observed in Woodhousei fowleri tadpoles reared in continuous dark (DD). To evaluate the mechanism by which DD delayed metamorphosis, lightcycle exposure was controlled and thyroxine (T4), melatonin, or drugs that alter prolactin (Prl) concentrations were given to Xenopus luevis tadpoles. It was hypothesized that exogenous melatonin would delay metamorphosis and increase body size, and that elevation of Prl concentrations would have effects similar to melatonin exposure. Xenopus luevis tadpoles were randomized to three light conditions [light/dark (LD, 12 h/12 h), DD, and continuous light (LL)] and subgroups in each light condition were treated with T4, melatonin, bromocriptine (Bro), haloperidol (Hal), or no drug. Each subgroup included 12 tadpoles. Drugs were administered in the water either continuously or daily from 07.00 to 19.00 h (Intermittent). Measurements of total length, leg length, and stage of metamorphosis were obtained at regular intervals. DD resulted in delayed metamorphosis, while LL did not. T4 accelerated metamorphosis as expected, countering the delaying effects of DD. In contrast to the hypothesis, melatonin accelerated metamorphosis and impaired body size compared to controls. Intermittent Hal also accelerated metamorphosis, while Bro delayed it. In DD, both T4 and melatonin led to increased tadpole size in contrast to their counterparts in LD or LL. Delayed metamorphosis in DD is not caused by increased melatonin production. Melatonin and Hal (as given in this study) accelerate metamorphosis. Melatonin acceleration of metamorphosis may occur through alteration of the concentration of prolactin.

A rise in plasma growth hormone (GH) after thyrotrophin-releasing hormone (TRH) and a striking reduction after dopaminergic drugs is present in acromegalic (&amp;amp;amp;#39;responder&amp;amp;amp;#39;) patients. We have investigated the GH response to dopaminergic stimuli in two conditions of animals and man, which, like acromegaly, are characterized by a TRH-induced GH rise, i.e. rats with electrolytic lesions of the median eminence (ME) and patients with hepatic cirrhosis. In addition, we have studied the TRH-induced GH rise in rats with ME lesions, in the cirrhotic patients and in a group of &amp;amp;amp;#39;responder&amp;amp;amp;#39; acromegalics before and after administration of dopaminergic drugs. In rats with ME lesions an infusion of dopamine (DA) neither modified baseline GH levels nor the TRH-induced GH rise. In five out of six cirrhotic patients oral administration of L-Dopa was followed by the usual rise in plasma GH. infusion of DA increased plasma GH levels in three out of seven cirrhotic patients and in four out of five subjects an earlier GH rise after TRH was seen. However, in the &amp;amp;amp;#39;responder&amp;amp;amp;#39; acromegalics, the infusion of DA, besides lowering baseline plasma GH, was capable of reducing the TRH-induced GH rise. Collectively these data indicate that the TRH-induced GH rise emphasizes defects in the neurohormonal links between the central nervous system and the anterior pituitary. Instead, the paradoxical fall of GH after dopaminergic drugs appears to be a prerequisite of acromegaly and may be attributable to receptors for DA located on the tumorous tissue.

Bromocriptine-QR (a quick-release formulation of bromocriptine mesylate), a dopamine D2 receptor agonist, is a US Food and Drug Administrration-approved treatment for type 2 diabetes mellitus (T2DM). A 3070-subject randomized trial demonstrated a significant, 40% reduction in relative risk among bromocriptine-QR-treated subjects in a prespecified composite cardiovascular (CV) end point that included ischemic-related (myocardial infarction and stroke) and nonischemic-related (hospitalization for unstable angina, congestive heart failure [CHF], or revascularization surgery) end points, but did not include cardiovascular death as a component of this composite. The present investigation was undertaken to more critically evaluate the impact of bromocriptine-QR on cardiovascular outcomes in this study subject population by (1) including CV death in the above-described original composite analysis and then stratifying this new analysis on the basis of multiple demographic subgroups and (2) ...

Objective: Because studies have shown some positive effects of the dopaminergic agent bromocriptine for improving verbal production in patients with nonfluent aphasia, we examined its effect in a patient with an atypical form of crossed nonfluent aphasia from a right hemisphere lesion. Design: Open-label single-subject experimental ABAB withdrawal design. Patient: A right-handed man who, after a right frontal stroke, developed nonfluent aphasia, emotional aprosodia, and limb apraxia. Intervention: Escalating doses up to 20mg of bromocriptine in 2 separate phases. Main Outcome Measures: We measured verbal fluency (words/min in discourse, Thurstone letter fluency), expression of emotional prosody, and gesture production. Results: The patient showed substantial improvement in both verbal fluency measures and no significant improvement in gesture or emotional prosody. Verbal fluency improvements continued in withdrawal phases. Conclusions: Our results are less likely caused by practice or spontaneous recovery because we observed little improvement in emotional prosody and gesture tasks. Verbal fluency improvements during treatment and withdrawal phases suggest that the effects of bromocriptine may be long-lasting in its influence on the neural networks subserving verbal initiation.

The bile salt export pump (BSEP) is an ABC-transporter expressed at the canalicular membrane of hepatocytes. Its physiological role is to expel bile salts into the canaliculi from where they drain into the bile duct. Inhibition of this transporter may lead to intrahepatic cholestasis. Predictive computational models of BSEP inhibition may allow for fast identification of potentially harmful compounds in large databases. This article presents a predictive in silico model based on physicochemical descriptors that is able to flag compounds as potential BSEP inhibitors. This model was built using a training set of 670 compounds with available BSEP inhibition potencies. It successfully predicted BSEP inhibition for two independent test sets and was in a further step used for a virtual screening experiment. After in vitro testing of selected candidates, a marketed drug, bromocriptin, was identified for the first time as BSEP inhibitor. This demonstrates the usefulness of the model to iden...

Background. The concurrent use of a postprandial insulin sensitizing agent, such as bromocriptine-QR, a quick release formulation of bromocriptine, a dopamine D2 receptor agonist, may offer a strategy to improve glycemic control and limit/reduce insulin requirement in type 2 diabetes (T2DM) patients on high-dose insulin. This open label pilot study evaluated this potential utility of bromocriptine-QR.Methods. Ten T2DM subjects on metformin (1-2 gm/day) and high-dose (TDID ≥ 65 U/day) basal-bolus insulin were enrolled to receive once daily (morning) bromocriptine-QR (1.6–4.8 mg/day) for 24 weeks. Subjects with at least one postbaselineHbA1cmeasurement (N=8) were analyzed for change from baselineHbA1c, TDID, and postprandial glucose area under the curve of a four-hour mixed meal tolerance test (MMTT).Results. Compared to the baseline, averageHbA1cdecreased 1.76% (9.74±0.56to7.98±0.36,P=0.01), average TDID decreased 27% (199±33to147±31,P=0.009), and MMTT AUC60–240decreased 32% (P=0.04)...

Bilateral gigantomastia is a rare condition, often associated with pregnancy that is characterized by a diffuse enlargement of both breasts. Here we present a case of a late 20s woman in her seven months pregnancy with a bilateral gestational gigantomastia associated with multiple breast lumps. Histological analysis revealed a fibroadenoma. Her prolactin level after caesarean delivery was found particularly high. A significant decrease in breast size was achieved with bromocriptine treatment in conjunction with a bilateral lumpectomy. This case report highlights the diversity of gigantomastia and emphasizes the importance of a tailored, multidisciplinary approach to the diagnosis and treatment of this condition.

Cystic prolactinomas are considered not amenable to dopamine agonist therapy. We present the results of dopamine agonist therapy in six patients with cystic prolactinomas. The inclusion criteria of patients were: (i) cystic macroadenomas with the cyst occupying more than 50% of the tumour volume; (ii) a serum prolactin value more than 150 ng/mL. All patients were males with a mean age of 35 years. The clinical presentations were erectile dysfunction in 66.6%, visual deficits in 50% and headache in 50% of patients. All patients were treated with bromocriptine only except one who was treated with both bromocriptine and cabergoline. The mean duration of follow up was 57.1 months. At the final follow-up 50% of patients had hormonal cure, 50% had radiological cure and 50% had reduction in the size of the tumour. Hence, it is appropriate to consider dopamine agonist therapy in patients with cystic prolactinomas before considering surgery.

There is growing evidence that the ergot-derived dopamine agonists cabergoline and pergolide can cause fibrotic cardiac valvulopathy. Data on other fibrotic reactions and nonergot-derived dopamine agonists are sparse. Aim of this study was to investigate whether there are signals that dopamine agonists are related to cardiac and other fibrotic reactions. We identified all reports of fibrotic reactions at the heart, lung, and retroperitoneal space associated with dopamine agonists within the US Adverse Event Reporting System database. Disproportionality analyses were used to calculate adjusted reporting odds ratios (RORs). For ergot-derived dopamine agonists (bromocriptine, cabergoline, pergolide), the RORs of all reactions under study were increased, whereas no such increases were observed for nonergot-derived drugs (apomorphine, pramipexole, ropinirole, rotigotine). Fibrotic reactions due to ergot-derived dopamine agonists may not be limited to heart valves. For nonergot-derived dopamine agonists, no drug safety signals were evident. © 2008 Movement Disorder Society