Dopamine (DA) is a principal natriuretic hormone that defends extracellular fluid volume from a Na load. Natriuresis is effected partly through inhibiting the proximal tubule Na/H exchanger NHE-3. Changes in NHE-3 phosphorylation is one mechanism by which NHE-3 activity is regulated.
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Involuntary visual spatial attention is captured when a salient cue appears in the visual field. If a target appears soon after the cue, response times to targets at the cue location are faster relative to other locations. However, after longer cue-target intervals, responses to targets at the cue location are slower, due to inhibition of return (IOR). IOR depends on striatal dopamine (DA) levels: It varies with different alleles of the DA transporter gene DAT1 and is reduced in patients with Parkinson's disease, a disease characterized by reduced striatal dopaminergic transmission. We examined the role of DA in involuntary attention and IOR by administering the DA D2 receptor-specific agonist bromocriptine to healthy human subjects. There was no effect of either DAT1 genotype or bromocriptine on involuntary attention, but participants with DAT1 alleles predicting higher striatal DA had a larger IOR. Furthermore, bromocriptine increased the magnitude of IOR in participants with low striatal DA but abolished the IOR in subjects with high striatal DA. This inverted U-shaped pattern resembles previously described relationships between DA levels and performance on cognitive tasks and suggests an involvement of striatal DA in IOR that does not include a role in involuntary attention.
In ten patients with amenorrhea-galactorrhea who had hyperprolactinemia, ovulation could not be induced clomiphene citrate or exogenous gonadotropins. Treatment with bromocryptine in eight of these patients resulted in suppression of PRL in all, cessation of galactorrhea and ovulation in seven and conception in five.
Pathophysiological mechanisms of peripartum cardiomyopathy are not yet completely defined, although there is a strong association with various factors that are already known, including pre-eclampsia. Peripartum cardiomyopathy treatment follows the same recommendations as heart failure with systolic dysfunction. Clinical and experimental studies suggest that products of prolactin degradation can induce this cardiomyopathy. The pharmacological suppression of prolactin production by D2 dopamine receptor agonists bromocriptine and cabergoline has demonstrated satisfactory results in the therapeutic response to the treatment. Here we present a case of an adolescent patient in her first gestation with peripartum cardiomyopathy that evolved to the normalized left ventricular function after cabergoline administration, which was used as an adjuvant in cardiac dysfunction treatment. Subsequently, despite a short interval between pregnancies, the patient exhibited satisfactory progress throughout the entire gestation or puerperium in a new pregnancy without any cardiac alterations. Dopamine agonists that are orally used and are affordable in most tertiary centers, particularly in developing countries, should be considered when treating peripartum cardiomyopathy cases.
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Treatment with bromocriptine + gonadotropin remains the simplest; the treatment protocol based on geserelin depot + gonadotropin proved to be more efficacious.
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A few cases of psychosis induced by clomiphene citrate have been described so far. However, data on the prevalence of psychotic symptoms among women treated for infertility are inconclusive. Still a little is known about possible psychiatric complications of medications used in assisted reproduction techniques (ART). We present a case of a patient who developed transient psychotic symptoms in the course of the in vitro fertilization procedures. To our kiiowledge, this is the first case of 'mid-stimulation psychosis', which has been observed during ART using clomiphene.citrate and bromocriptine. The aim of this study is to describe the determinants ofpharmacotherapy undertaken in ART,.which can result in the development of psychotic symptoms.
A 68-year-old male patient presented with visual impairment due to a large pituitary tumor. After transsphenoidal adenomectomy the elevated serum FSH levels were lowered but not normalized. Deterioration of the vision was detected five years later and tumor regrowth was evidenced. The patient was treated with the long-acting and repeatable form of bromocriptine (Parlodel-LAR). Three days after the first intramuscular injection it already resulted in an important improvement of the visual field defects. Serum FSH concentration was suppressed during a prolonged period, but no change in the size of the pituitary adenoma was recorded on CT scan. Long-term oral treatment with bromocriptine resulted in a sustained suppression of the serum FSH levels, without further visual improvement, but with a significant reduction of the volume of the adenoma. The rapid and prolonged effect of Parlodel-LAR upon the FSH secretion, with a possible correction of the visual field defects and a reduction of the tumor mass, could make this medication appropriate as adjunctive treatment in some gonadotroph cell adenomas.
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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.
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The response of prolactin receptor and lactose synthetase to suppression of plasma concentrations of prolactin was examined in normal and occluded (teat-sealed) mammary glands of Sprague-Dawley rats, Rats, with mammary glands unilaterally occluded, were given bromocriptine (2.5 mg/kg per 12 h) between 5 and 8 post partum. Bromocriptine reduced plasma prolactin concentrations from 460.4 +/- 120.8 (mean +/- s.e.m.) to 2.56 +/- 0.89 ng/ml within 12h whilst concentrations in control rats were 553.4 +/- 110.25 ng/ml. Lactose synthetase activity declined rapidly, within 24h, in occluded glands of both groups but was maintained for 24 h in normal glands of bromocriptine-treated rats and decreased thereafter. Prolactin receptors also declined significantly within 24h in occluded glands. Desaturation of the prolactin receptor by bromocriptine treatment in vivo was compared with desaturation by exposure of membranes to MgCl2 in vitro. Both treatments enhanced prolactin binding but the increase after treatment with MgCl2 may have been partly artefactual since there was a selective loss of protein from the membranes. These results indicate that the prolactin receptor in rat mammary gland may be maintained after acute suppression of prolactin secretion.
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The prevalence of known cases of acromegaly in Northern Ireland in 1984 was 6.3 per 100,000 population. The incidence of newly-diagnosed cases over the preceding 25 years was 5.5 patients per year, or 0.4 patients per 100,000 population per year. This rate would be equivalent to about 200 new cases per year in the United Kingdom. Four options have been available to most of these patients--surgical hypophysectomy (transfrontal or transsphenoidal), pituitary radiotherapy (usually external cobalt beam), drug treatment with bromocriptine, or no treatment. Choice of treatment has been mainly influenced by tumour size, with the larger pituitary adenomas having surgery initially. No single form of treatment has been successful in achieving a clinical remission or cure in more than a minority of cases. The most successful outcome has been where total pituitary ablation has been achieved. Life-table analysis for the whole group shows life expectancy which is not markedly different for that of an age-matched population from Northern Ireland. Morbidity related to long term osteoarthritis and treatment complications remain a major problem. The incidence of malignant tumours is higher than would be expected.
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The neuroleptic malignant syndrome (NMS) occurs as a hypersensitivity response in certain patients exposed to neuroleptics. It is a relatively rare, but potentially lethal complication, the incidence of which may have been underestimated. Recent interest in NMS has arisen due to the recognition that specific therapy may now be available. This review summarises the clinical features and discusses recent ideas regarding aetiology and treatment.
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Five patients, 3 women and 2 men, with macroprolactinomas characterized by extrasellar extension and basal plasma prolactin levels ranging from 4.6 to 102 U/l received six monthly injections of 50-100 mg Parlodel LAR, an injectable long-acting repeatable form of bromocriptine. The following observations were made: 1. Plasma prolactin levels fell dramatically in all patients and values in the normal range were obtained in 3 patients. 2. In all patients, the onset of tumour reduction was visible on CT scans made one week after the first Parlodel LAR injection. After six Parlodel LAR injections, tumour size was reduced by more than 75% in 3 patients and by 50-75% in two patients. 3. Diminished visual acuity (one patient), bitemporal hemianopia (2 patients), and oculomotor and trochlear nerve dysfunction (one patient) were restored to normal after the first Parlodel LAR injection. 4. Hypogonadism normalized in 2 patients and improved in one patient, whereas plasma gonadotropins remained low in the 2 postmenopausal women. In one patient with hypothyroidism and hypocorticism, thyroid and adrenal functions normalized. It is concluded that bromocriptine retard (50-100 mg monthly) is a useful alternative for oral treatment of patients with prolactinomas, especially in those patients with compliance problems on oral bromocriptine therapy.
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Slices for immunohistochemical pathology were randomly selected from 37 paraffin-embedded prolactinoma tissue sections. LC3 was detected by immunohistochemistry. GH3 and MMQ cells were treated by BRC and/or rapamycin (RAPA). Cell viability and the cell cycle were measured by CCK-8 and flow cytometry, respectively. ELISA measured prolactin secretion. Protein expression was detected by Western blot or immunofluorescence.
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Seventy-three hyperprolactinaemic women were followed up with radiographic examinations (lateral and posteroanterior coned down views) of the sella turcica for 5 to 13 years during which time all but one had received treatment with bromocriptine. Progression of the sellar asymmetry occurred in 25 women (7 during pregnancy), 14 had regression of their changes in the pituitary fossa while 34 did not show any changes in the configuration of the sella turcica. Prolactin levels in serum, duration of bromocriptine therapy or sellar configuration could not predict later radiographic progressive or regressive changes of the sella turcica. The clinical course was benign in the majority of the women with signs of prolactin-producing adenomas. The risk of serious tumour enlargement seems to be very small. We were not able to demonstrate any parameter which could predict the growth or shrinkage of the tumour. Routinely repeated radiographic sellar examinations are unnecessary in the vast majority of hyperprolactinaemic women.
Eight monkeys developed a severe parkinsonian syndrome after i.v. administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with bromocriptine (5 mg/kg) relieved the parkinsonian symptoms, but the efficacy of this treatment appeared to decrease slightly with time. The addition of SKF38393 (5 mg/kg) to the bromocriptine treatment in four monkeys prevented and even reversed the tendency to decreased efficacy with an increased response in three out of four animals. Neither of these two treatments induced dyskinesia in these monkeys. Dopamine D1 and D2 receptors, assayed in the caudate nucleus, the putamen and nucleus accumbens with [3H]SCH 23390 and [3H]spiperone binding respectively, were not significantly different in MPTP monkeys treated with bromocriptine or with bromocriptine plus SKF38393. Monkeys in the two treatment groups had a similar extent of denervation of the striatum and accumbens as assessed by the content of dopamine and its metabolites. These results suggest that in MPTP monkeys, the behavioral response to the D2 agonist bromocriptine can be enhanced by concomitant activation of the D1 receptors while this combination of agonists does not induce dyskinesia. The addition of the D1 agonist does not appear to cause further alteration of the D1 or D2 receptors.
We performed a case-controlled analysis on the effectiveness of dantrolene and certain dopamine agonists--bromocriptine, amantadine 3,4-dihydroxyphenylalanine, (DOPA)--for the neuroleptic malignant syndrome (NMS). This was based on a review of all known published studies using as controls those cases not treated with these drugs and/or electroconvulsive therapy. In this control group, the NMS-related death rate was 21 percent. Dantrolene alone reduced the death rate to 8.6 percent, bromocriptine alone to 7.8 percent, and amantadine alone to 5.9 percent. We also stratified patients into five levels of severity based on state of consciousness and temperature and showed that the relative reduction in death rate held up at all levels. The dopamine agonists and dantrolene have a therapeutic effect independent of each other.
Women are most susceptible to psychotic reactions during the postpartum period, a time of intense psychological and physiological stress. Mania and depression are particularly common at this time, especially in women with past or family histories of major or minor affective disorders, specifically cyclothymia and dysthymia. Close attention after childbirth is warranted to alleviate and prevent these episodes in such women. Sympathomimetic drugs such as bromocriptine and the over-the-counter diet aids, which are linked to the induction of manic episodes, are frequently used in the puerperal period and may act as catalysts. This case report documents a postpartum manic episode in a cyclothymic woman who was prescribed bromocriptine, a dopamine agonist, for prevention of lactation.
The paper deals with a Prolactinoma case appearing as a swelling of the rhinopharynx, which developed cephalgia related to the nasal blockade as solitary symptom. Recite of the main clinical characteristics, diagnostic process and therapeutics of this condition. The differential diagnosis with other tumors situated in the sellar space or in the rhinopharynx, is also considered.
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The case presented here describes the clinical evolution of a malignant prolactinoma with occurrence of intra- and extra-cranial metastases. In this case, the presence of dopamine 2 receptor (D2R) was studied at the mRNA and protein level, in order to understand the pathological background of the resistance to treatment with different dopamine agonists.
Microdialysis, binding and behavioural studies have shown that the dopaminergic system plays a role in antidepressant treatment.
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Ropinirole is a non-ergot dopaminergic agonist with a high affinity for D2 dopaminergic receptors which improves the symptoms of Parkinson's disease (PD) and delays the appearance of motor complications. It is different to the first generation of dopaminergic agonists in that, because it lacks an ergolinic structure, it does not have the side effects that usually appear with the use of this pharmacological group.
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Despite the availability and application of more effective antihypertensive drugs over the past 3 decades, hypertension continues to be a major risk factor for the development of premature cardiovascular disease. Moreover, failure to elucidate the pathogenesis of essential hypertension, noncompliance, and difficulties in defining the appropriate level of blood pressure elevation requiring therapy, continue to mitigate against the adequate control of hypertension. Some of these problems may be overcome by the availability of depot forms of antihypertensive medication or implantable drug delivery systems, or by the use of several recently developed antihypertensive drugs. These include dopaminergic agonists, selective alpha-adrenergic agents, calcium antagonists, medullary neutral lipids, gamma-aminobutyric acid agonists, and inhibitors of renin or phenethylamine N-methyl-transferase. In addition, the potential involvement of morphinomimetic peptides, prostaglandins, tonin, and bradykinin in blood pressure control or certain hypertensive states suggests that drugs developed to block or potentiate the actions of these substances may have important therapeutic applications.
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She was treated with local debridement, bromocriptine, antibiotics and blood transfusion with good results. The pregnancy however terminated at 27 weeks of gestation.
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One of the most important causes of anticancer treatment failure is the development of multidrug resistance (MDR). The main characteristics of tumor cells displaying the MDR phenomena are cross-resistance to structurally unrelated cytotoxic drugs having different mechanisms of action and the overexpression of the MDR1 gene, which encodes a transmembrane glycoprotein named P-glycoprotein (P-gp). This study evaluated whether bromocriptine, a D2 dopaminergic receptor agonist, influenced anticancer drug cytotoxicity and P-gp activity in a P-gp-expressing cell line compared to a non-expressing subline. The K(i) values for P-gp of cyclosporine and verapamil were 1.09 and 540 microM, respectively, and that of bromocriptine was 6.52 microM in a calcein-AM efflux assay using porcine kidney epithelial LLC-PK1 and L-MDR1 cells, overexpressing human P-gp. Bromocriptine at 10 microM reduced the IC50 of doxorubicin (DXR) in K562-DXR from 9000 to 270 ng/ml and that of vincristine (VCR) in K562-VCR from 700 to 0.30 ng/ml, whereas the IC50 values of DXR and VCR in the K562 subline were only marginally affected by these drugs. Bromocriptine restored the anticancer effect of DXR, VCR, vinblastine, vinorelbine and etoposide on MDR-tumor cells overexpressing P-gp. These observations suggest that bromocriptine has the potential to reverse tumor MDR involving the efflux protein P-gp in the clinical situation.
Injection of an ovulation-blocking dose of pentobarbitone sodium given in the early afternoon of pro-oestrus in rats decreased follicular oestradiol production in vitro the next day (2.42 +/- 0.11 ng/4 h/follicle in pro-oestrous rats, 0.49 +/- 0.04 ng/4 h/follicle in pentobarbitone-treated rats). Pentobarbitone, given 1 day earlier (at dioestrus II), prevented the increase in oestradiol production that normally occurs between di-oestrus II and pro-oestrus. Injection of a subovulatory amount of hCG (0.5 i.u.) given after pentobarbitone injection inhibited the decrease in follicular oestradiol production induced by pentobarbitone. The pentobarbitone-induced decrease in oestradiol production was also prevented by bromocriptine (1 mg) given at di-oestrus II (15:00 h) and pro-oestrus (09:00 h). Bromocriptine is an effective inhibitor of prolactin secretion and this suggests therefore that the decrease in follicular oestradiol production after pentobarbitone is due to the preovulatory surge of prolactin. However, pretreatment with bromocriptine also inhibited the effect of pentobarbitone on oestradiol production when pentobarbitone was given at di-oestrus II. Moreover, when ergocornine (another inhibitor of prolactin secretion) was used instead of pentobarbitone to block ovulation, follicular oestradiol production was also decreased the next day. In contrast to bromocriptine, ergocornine was not able to prevent the pentobarbitone-induced decrease in follicular oestradiol production. These results indicate that the decrease in follicular oestradiol production after pentobarbitone injection is due to inhibition of the serum concentrations of LH rather than the preovulatory surge of prolactin. How bromocriptine (but not ergocornine) prevents the pentobarbitone-induced decrease in oestradiol production is not clear.
Significantly more embryos were cleaved and had superior morphology in group 1 than group 2. Clinical and ongoing pregnancy rates per oocyte pick-up were significantly higher in group 1 (42% and 38%, respectively) than group 2 (24% and 21%, respectively). The mean PRL concentration was significantly higher in the group 1 than group 2. A significant correlation between the number of superior embryos and PRL concentrations was observed in group 1, but not in group 2.
The clinical use of bromocriptine (2.5 mg twice daily) was investigated in 40 women attending an infertility clinic and presenting with secondary amenorrhoea (18) or with ovarian dysfunction (22) which had failed to respond to anti-oestrogen therapy. Patients in each group were sub-divided into those with raised and those with normal prolactin levels, and re-examined at 3 and 12 months after the start of treatment. The results confirmed that bromocriptine is effective in the treatment of hyperprolactinaemic states whether there is amenorrhoea or not. Moreover, in cases of ovarian dysfunction as well as of amenorrhoea where the prolactin levels were within the normal range, there was evidence to suggest that bromocriptine can be associated with a return of ovulation, although the mechanism by which it might do so still needs evaluation.