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Bromocriptine stimulates testosterone production by mouse testes in vitro.

The production of testosterone (T) by decapsulated mouse testes in vitro was significantly stimulated by 2-Br-alpha-ergocriptine (bromocriptine) at concentrations ranging from 1 ng/ml to 5 microgram/ml. In the presence of a low dose of human chorionic gonadotropin (hCG), bromocriptine produced a further increase in T production, whereas in the presence of a high concentration of hCG it was ineffective. It is suggested that a direct stimulatory effect of bromocriptine on testicular steroidogenesis may contribute to its therapeutic effects in hyperprolactinemic men.

Animals↗

Bromocriptine mesylate for prevention of postpartum lactation.

The efficacy and safety of bromocriptine mesylate in preventing postpartum breast engorgement and milk secretion were evaluated in 420 normal puerperal women. The usual dose was 2.5 mg twice a day for 14 days. Complete inhibition of the target symptoms was obtained in 97% (409 of 420) of the women after 5 days of therapy. Of 370 women who completed 14 days of therapy, 73.5% (272) were completely symptom free, and the remainder showed only grade I or grade II breast engorgement and secretion. Side effects, primarily nausea, vomiting, and dizziness, were experienced by 3% of the women, and 7% reported rebound engorgement and secretion. It was concluded that bromocriptine is safe and efficacious for the stated indication. Moreover, bromocriptine's apparent lack of thromboembolic complications and low incidence of rebound effects suggest possible advantages over other pharmacologic preparations, ie, estrogen-containing drugs, currently used to prevent postpartum lactation.

Adult↗

Failure of bromocriptine to modify the response to metyrapone in normal subjects.

In order to study the role played by the dopaminergic system on the secretion of ACTH, we evaluated the influence of bromocriptine on the response to metyrapone. Levels of serum cortisol and 11-deoxycortisol and of urinary 17-OH-corticosteroids and 17-ketosteroids were measured both before and after stimulation with metyrapone in ten normal adults. This was followed by a week of administration with bromocriptine (5 mg/die) after which the above measurements were repeated. The results obtained did not differ significantly. Thus it may concluded that, under these conditions and at this dose, bromocriptine does not modify the response to metyrapone.

17-Hydroxycorticosteroids↗

Respiratory effects of amantadine and bromocriptine and their interaction with haloperidol in anesthetized rats.

Amantadine and bromocriptine and caused a dose-related respiratory stimulation in anesthetized rats; in the case of bromocriptine, the highest dose used induced a stimulatory response which was preceded by a decrease in respiratory frequency. The effects were markedly counteracted by the previous administration of haloperidol. It is proposed that the dopaminergic system is involved, at least in part, in the respiratory action of amantadine and bromocriptine.

Amantadine↗

Medical management of acromegaly with bromocriptine. Effects of continuous treatment for over three years.

Eighty-seven patients with active acromegaly were treated with bromocriptine for periods of up to 42 months. On treatment, 82 of these patients noted a rapid alleviation of one or more symptoms of their disease. In 67 patients, the mean growth hormone level of four values taken through the day fell by 14 mu/L or more, or became undetectable. Eighty patients have been treated for over 12 months and this suppression was maintained. Improvement in abnormal glucose tolerance occurred in 25 out of 29 diabetics and tolerance became normal in 19. Bromocriptine is of great value in cases in which surgery or radiotherapy has not been completely effective or as interim treatment until the full effect of other therapy has taken place. However, the long-term effect of high doses of bromocriptine is not yet known.

Acromegaly↗

The effect of pretreatment with prostaglandin E2 (PGE2), verapamil, nicergoline and bromocriptine on ischemia-reperfusion injury of rat liver in vivo.

Ergot alkaloids possess some properties potentially beneficial in ischemia of organs. Therefore the effect of pretreatment by nicergoline and bromocriptine was established in ischemia-reperfusion injury of rat liver. PGE2 and verapamil were used as comparative agents. Hepatic ischemia (60 min) of anesthetized rats was induced by clamping of vessels supplying the median and left lateral lobe. Tested drugs were given i.v. 2 or 5 min prior to inducing ischemia. ALT and AST activities in serum two hours after the end of ischemia were used as markers of hepatocellular injury. Only PGE2 (0.1 mg.kg-1) pretreatment minimized the postischemic rise of both ALT and AST activities. Pretreatment with various doses of nicergoline (1 or 4 mg.kg-1), bromocriptine (1 or 4 mg.kg-1) and verapamil (0.9 or 4.5 mg.kg-1) did not influence significantly serum transaminases activities after ischemia. Bromocriptine (4 mg.kg-1) given together with PGE2 did not improve a protective effect against ischemia achieved by the administration of PGE2 (0.1 microgram.kg-1).

Animals↗

[Hyperprolactinemic amenorrhea:treatment with cabergoline versus bromocriptine. Results of a national multicenter randomized double-blind study].

OBJECTIVES: Cabergoline is a new, long-acting D2 agonist, highly effective in suppressing prolactin and restoring gonadal function in hyperprolactinaemic amenorrhoea. This study compares its efficacity and safety with that of the reference compound, bromocriptine. METHODS: A prospective study involved 21 French Centres and 120 women, with hyperprolactinaemic amenorrhoea, randomized to either cabergoline (CAB 0.5-1 mg twice weekly) or bromocriptine (BRC 2.5-5 mg twice daily). Treatment is given under double-blind conditions for the first 8 weeks, and subsequently in open conditions in further 16 weeks with dose adjustments according to response. Patients were assessed for biochemical and clinical efficacy and drug safety (adverse symptoms and biology). RESULTS: Normoprolactinaemia was achieved in 56/60 (93.3%) taking CAB and 27/58 (48.2%) taking BRC (p < 0.0001). Ovulatory cycles or pregnancy were recorded in 71.6% and 48.2% of patients (p = 0.001). Prolactin suppression to below 50% of the baseline value was observed in 1.6% and 15.5% (p = 0.007). Adverse symptoms were recorded in 31/60 (51.6%) and 40/58 (69.2%) patients respectively in the double-blind period, and 53.3% versus 65.5% for the full course of the study. There were significantly fewer gastro-intestinal symptoms in the CAB group, 36.6% versus 84.5% (p < 0.0001). CONCLUSION: Cabergoline is a new prolactin-lowering drug, more effective and better tolerated with fewer gastrointestinal symptoms than the reference compound, bromocriptine.

Adolescent↗

[Response of growth hormone to sandostatin and bromocriptine and prognostic value of prolactin levels in serum and thyroliberin test in patients with active acromegaly].

Usefulness of determination of blood serum prolactin concentration and the result of thyroliberin (TRH) stimulation test for predicting the magnitude of growth hormone (GH) response to the administration of sandostatin and bromocriptine has been evaluated in 14 patients with active acromegaly. No relation was found between the occurrence of hyperprolactinemia and the response of GH to the administration of sandostatin and bromocriptine. Analysis of GH secretion after TRH administration made possible the selection of a group of acromegalic patients with paradoxical increase in GH secretion in response to TRH in whom the administration of sandostatin caused a significant decrease in blood serum concentration of GH following the administration of sandostatin. TRH stimulation test had, however, no value in predicting the effect of bromocriptine on GH secretion.

Acromegaly↗

[Beneficial effect of bromocriptine in a patient with malignant syndrome and hepatic dysfunctions].

A 39 year-old male, diagnosed as meningoencephalitis, was admitted because of the development of malignant syndrome. This syndrome appeared to have resulted from anti-psychotic drugs given to relieve excitement and insomnia. As he had hepatic dysfunctions, we could not administer dantrolene further. Therefore, we gave bromocriptine to ameliorate the symptoms such as muscle rigidity or hemodynamic perturbations. Thereafter, the patient gradually became stable in hemodynamics and in other symptoms. In addition, a further deterioration in hepatic functions did not occur with administration of bromocriptine. The case suggests that in patients with malignant syndrome associated with hepatic dysfunctions, bromocriptine could be a first choice as a pharmacological treatment of the syndrome.

Adult↗

[Treatment of rheumatoid psoriasis with bromocriptine].

Non-steroid anti-inflammatory drugs and/or gold salts were unsuccessful alone in providing symptom relief in three men with rheumatoid psoriasis. All three were treated with bromocriptine (5 mg/d in 2 doses) after verification of normal baseline and protirelin-stimulation prolactin levels. There was a beneficial effect in nocturnal pain relief, morning stiffness, the Lee and Ritchie scores and biological markers of inflammation. Two of the patients were able to return to regular work occupation after 15 and 45 days. In the third patient, bromocriptine was discontinued due to nausea and dizziness but was reintroduced successfully in fractionated doses after recurrence of the symptomatology. Treatment was continued without secondary adverse effects for 3 to 9 months providing continued symptom relief. Bromocriptine can be an effective adjuvant for the management of rheumatoid psoriasis.

Adult↗

Bromocriptine is ineffective in the treatment of chronic nonfluent aphasia.

The effect of bromocriptine on chronic nonfluent aphasia was investigated in 4 patients suffering from a stroke 24 to 35 months before the onset of this study (average 29 months). Two patients had Broca, one had global and the other transcortical motor aphasia. CT-scans demonstrated anterior-posterior infarctions in 3 patients and anterior infarction in one. Bromocriptine was given initially at a dosage of 10 mg/day, and of 25 mg/day during the follow ups. By means of aphasia tests, bromocriptine was found to be ineffective for the treatment of any symptoms of chronic nonfluent aphasia.

Adult↗

[Use and value of the therapeutic neuroleptic-bromocriptine combination in schizophrenia].

Use and interest of therapeutic association bromocriptine-neuroleptic in schizophrenia. Twelve schizophrenic patients were treated by bromocriptine (7.5 mg.day) and neuroleptic. After one month, patients on this treatment showed a mean improvement of 29% on the total score of the positive and negative symptom scale. This results suggest that therapeutic association bromocriptine-neuroleptic may be used for schizophrenic patients.

Adult↗

[A novel method of ovarian stimulation for in vitro fertilization (bromocriptine-rebound method) increases developmental potential of oocytes and pregnancy rate].

A novel method of ovarian stimulation for IVF is reported. Endocrine-normal ovulatory women with a history of unsuccessful IVF attempts by means of a long protocol of a GnRH agonist/hMG regimen (L regimen) were studied. Ovaries were stimulated by the three regimens described below. The bromocriptine-rebound (BR) regimen consisted of bromocriptine (B) 2.5mg/day administered daily beginning on day 4 of the preceding cycle and buserelin acetate administered beginning in early high phase. Administration of B was discontinued in the low phase of the IVF cycle and daily administration of hMG was begun 7 days later. HCG was administered when dominant follicles reached 16-18 mm in diameter. The bromocriptine-continuous (BC) regimen was the same as the BR regimen, except that B was administered until the administration of hCG. The L regimen was the same as the BR regimen, except that no B was administered. The pregnancy rate per oocyte retrieval was significantly higher on the BR regimen (56% in 70 cycles) than the L regimen (33% in 46 cycles), and lowest on the BC regimen (29% in 7 cycles). The rate of fertilization and cleavage per oocyte and the proportion of morphologically-good embryos were significantly higher on the BR regimen (59.1% and 57.3%, respectively) than the L regimen (46.3% and 48.0%, respectively), and lowest on the BC regimen (49.0% and 41.7%, respectively). Serum PRL concentrations (ng/ml) at the time hMG was started were 14.9 +/- 1.5, 7.9 +/- 1.7 and 2.5 +/- 0.7 on the BR, L and BC regimens, respectively. The results of this study show that the BR regimen increases the developmental potential of oocytes and the pregnancy rate, probably because of increasing serum PRL levels to within the normal range.

Adult↗

[Blood prolactin under the effect of protirelin in spondylarthropathies. Treatment trial of 4 cases of reactive arthritis and 2 cases of psoriatic arthritis with bromocriptine].

Prolactin radioimmunoassay was carried out before and 15, then 30 min after intravenous infusion of protireline (0.2 mg) in 3 groups of male patients: 7 with reactive arthritis (HLA B27: 6; age: 25 +/- 6.3 yr), 13 with ankylosing spondylitis (HLA B27: 11; age: 33.2 +/- 14.7 yr), 5 with psoriatic arthritis (HLA B27: 1; age: 28.8 +/- 6.3 yr). The same test was carried out in sex-age-body mass index matched controls. Only the patients with reactive arthritis presented dynamic hyperprolactinaemia 15 and 30 min after protireline infusion and none of ankylosing or psoriatic arthritis groups. A complete failure of bromocriptine was observed in reactive arthritis. In 2 cases of psoriatic arthritis, adding bromocriptine to gold salts and nonsteroidal anti-inflammatory drug was followed by a drastic efficacy with spectacular improvement in clinical, biological and occupational status. Because none of the cases had hyperprolactinaemia, bromocriptine acted probably had an intrinic anti-inflammatory effect independent of its antiprolactinic effect.

Adult↗

Long-term follow-up of women with amenorrhea-galactorrhea treated with bromocriptine.

The present study is aimed at investigating whether long-term use of bromocriptine on patients affected by amenorrhea and galactorrhea may improve the clinical picture after discontinuation of treatment. For this reason 26 patients with amenorrhea and galactorrhea have been studied. Sixteen had high PRL values and 10 were normoprolactinemic. The normoprolactinemic patients underwent a TRH test. All the patients underwent computed skull axial tomography (CT scan) and were treated with bromocriptine, at a daily dosage variable from 2.5 to 10 mg for an average period of 26 months. After discontinuation of treatment, follow-up was carried-out for 20 months. Eighty-seven percent of the patients affected by amenorrhea, galactorrhea and hyperprolactinemia had regular menses, in 75 of the patients galactorrhea completely disappeared. Of the ten patients with normoprolactinemic amenorrhea and galactorrhea, only those who positively responded to the TRH test had regular menstruation and showed disappearance of galactorrhea. Upon discontinuation of treatment amenorrhea recurred in 68% of the cases whereas galactorrhea recurred in 80%. CT scans revealed disappearance of 3 microadenomas and reduction in size of the macroadenoma. Long-term use of bromocriptine represents the first choice treatment for the syndrome of galactorrhea-amenorrhea. In case of relapse, treatment must be continued for an undefined period of time.

Adenoma↗

[Seizures as a late complication of bromocriptine therapy in patients with prolactin-producing macroadenomas: correlation between lateral extension of the adenoma and seizure onset].

Seizures have been reported as a late complication of medically treated prolactin-producing macroadenomas with lateral extension. Nine prolactin-producing macroadenomas with lateral extension to the cavernous sinus were treated with bromocriptine alone. In all cases, rapid decrease of serum prolactin level was recognized and in eight cases, evidence of tumor shrinkage on CT or MRI was demonstrated. During medical treatment, symptomatic seizures occurred in three cases. MRI showed small residual tumors on the medial surface of the temporal lobe in all these patients. Additionally, a hypointense signal on both T1- and T2-weighted images was recognized around the residual tumor. It was consistent with hemosiderin, a result of intratumoral hemorrhage caused by bromocriptine. On the contrary, the remaining six patients without seizures during treatment did not show abnormal hypointense signals on the medial surface of the temporal lobe. Seizures occur with a high incidence as a late complication of medical treatment of prolactin-producing macroadenomas with intradural supracavernous extension. The patients with seizure show hemosiderin deposit, which may be the trigger of the seizure, within the medial surface of the temporal lobe after bromocriptine therapy.

Adenoma↗

Long-term treatment of galactorrhoea and hypogonadism with bromocriptine.

Seventeen women and four men with galactorrhoea and associated hypogonadism have been treated with bromocriptine for 2 to 28 months. In 18 patients the gonadal status became normal as the galactorrhoea improved. The gonadally unresponsive patients had either pituitary tumours or premature menopause. Prolactin levels fell with treatment; withdrawal of the drug was associated with an increase in serum prolactin and a recurrence of the galactorrhoea and hypogonadism. Two patients tried to become pregnant on treatment and both succeeded. Raised prolactin levels appear to block the actions of the gonadotrophins at a gonadal level rather than prevent their synthesis or release; lowering prolactin secretion with bromocriptine allows resumption of normal gonadal function. Bromocriptine appears to be the treatment of choice for inappropriate lactation in association with hypogonadism on a long-term basis.

Bromine↗

Bromocriptine improves glycaemic control and serum lipid profile in obese Type 2 diabetic subjects: a new approach in the treatment of diabetes.

Bromocriptine, a potent dopamine D(2) receptor agonist, has been shown to reduce insulin resistance, glucose intolerance and hyperlipidaemia in both numerous animal studies and in Phase II studies. Bromocriptine has been used worldwide for over 20 years to treat Parkinson's disease, macroprolactinoma and other disorders; it has been found to be generally safe. We therefore investigated the possible beneficial effects of Ergoset(R) (Ergo Science Corp.), a new quick release formulation of bromocriptine, on glycaemic control and serum lipid profile in obese Type 2 diabetic subjects in two large Phase III studies. A large, randomised, double-blind placebo-controlled study was conducted in which Ergoset was given once daily at 8 am. (4.8 mg maximum dose) for 24 weeks as adjunctive therapy to sulphonylurea (485 subjects) to obese Type 2 diabetics held on a weight- maintaining diet. Treatment efficacy parameters included change from baseline in glycated haemoglobin A(1c) (HbA(1c)), fasting and post-prandial serum glucose, insulin, triglyceride and free fatty acid levels. Baseline glycated haemoglobin, fasting glucose, insulin, triglyceride and free fatty acid levels did not differ between treatment groups. and on average were 9.4 +/- 0.05%, 222 +/- 2 mg/dl, 24 +/- 1 µU/ml, 248 +/- 11 mg/dl, and 850 +/- 32 µEq/l, respectively. A similarly designed study of Ergoset as monotherapy in Type 2 diabetics (154 subjects) with similar baseline clinical characteristics was conducted. Addition of Ergoset treatment to sulphonylurea reduced percent glycated HbA(1c) by 0.55 (P < 0.0001) (approximately 1.0 for responders, 65% of population), fasting and post-prandial glucose by 23 and 26 mg/dl (P < 0.0002), fasting and post-prandial triglycerides by 72 and 63 mg/dl (P < 0.005) and fasting and post-prandial free fatty acids by 150 and 165 µEq/l (P < 0.05), relative to placebo. Twelve percent of all Ergoset subjects, compared to 3% of placebo subjects, withdrew from the study due to adverse events. The most common events causing withdrawal were nausea, dizziness, asthenia, and rhinitis (representing 4.5, 3.3, 2.0, and 0.8% of the total Ergoset populations, respectively). The incidence of serious adverse events did not differ between Ergoset- (3.4%) and placebo- (4.3%) treated subjects. Ergoset as monotherapy also improved glycaemic control (0.56 HbA(1c) decrease relative to placebo after 24 weeks of treatment; P < 0.02). Once daily Ergoset treatment improves glycaemic control and serum lipid profile and is well-tolerated in obese Type 2 diabetics.

Journal Article↗