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Bromocriptine: effect on serum prolactin and growth hormone in psychogeriatric hospital patients.

Serum prolactin (PRL) and human growth hormone (HGH) were assessed before, and three hours after oral administration of 2.5 mg of bromocriptine in 39 hospitalized geriatric patients with organic brain syndrome. Serum PRL concentrations decreased significantly irrespective of initial values (also in the 7 geriatric control subjects), but HGH levels were low in all patients and did not change during the three hours after administration of bromocriptine. Closer scrutiny of the HGH responses to bromocriptine in 5 patients and 5 controls showed that the serum HGH response was more variable among the patients than among the controls. The findings are discussed in relation to neuroendocrine changes associated with aging, institutional living, and mental disease.

Aged↗

Transfer of bromocriptine across the blood-brain barrier in man.

The transfer of 14C-bromocriptine across the blood-brain barrier was studied in 10 patients using the double indicator single injection method. The extraction (E) of bromocriptine was 8 % (quartiles: 6 and 14 %). Based on the results the cerebral uptake velocity of bromocriptine was calculated assuming constant arterial drug concentration. Its T 1/2 was found to be 12--24 minutes, depending on the tissue-blood partition coefficient.

Adult↗

Bromocriptine treatment of depressive disorders. Clinical and biochemical effects.

Fifteen depressed patients were treated with increasing doses of bromocriptine in an open study. Twelve were treated for 5 weeks (final dose 20-60 mg daily) and nine of these recovered almost completely. As expected from a dopamine agonist, bromocriptine decreased the level of homovanillic acid (HVA) in cerebrospinal fluid (CSF) by 15% (P less than 0.05) and 23% (P less than 0.01) after 2 and 5 weeks of treatment, respectively. After 2 but not after 5 weeks of treatment there was also a small but significant decrease (13%; P less than 0.001) of the noradrenaline metabolite HMPG in CSF. Although there was no mean effect on 5-HIAA in CSF, there was a significant relationship between the HVA and 5-HIAA levels (as % of pretreatment level) both after 2 and 5 weeks of treatment (r = 0.96 and r = 0.62, respectively). This may indicate that the drug has an effect on the serotonin system secondary to the dopamine receptor stimulation. The amelioration of depression was not related to HVA, but did correlate to HMPG in CSF (r = 0.65; P less than 0.05) both metabolites measured before treatment. These results indicate that bromocriptine may have antidepressant effects possibly mediated through the noradrenergic system rather than the dopaminergic system.

Adult↗

Prolactin and 3-methylcholanthrene induced cervical carcinoma. Effect of bromocriptine.

Female mice of the NMRI strain were injected with estradil for the first five days after birth (estrogenized animals) and ovariectomized at the ages of 6-9 weeks. One week later, a cotton thread impregnated with 3-methylcholanthrene was inserted into the uterine cervix. Starting on the day of insertion of the thread, and for a further 6 days, the females were injected with estradiol (E2), ovine prolactin (P), or 2-bromo-alpha-ergokryptine mesylate (bromocriptine). Controls were injected with vehicles only. The animals were killed 4 or 8 weeks after insertion of the thread, and the uterine cervix was serially sectioned. A combined treatment with E2 and P resulted in an increased incidence of invasive epithelial lesions in the uterine cervix. This incidence was higher than in controls or females injected with either hormone separately. Bromocriptine reduced the incidence of invasions, and this reduction with either hormone separately. Bromocriptine reduced the incidence of invasion, and this reduction could not be restored to the contrl level by a simultaneous treatment with E2 anrogenized females was higher than that reported in an earlied study using non-estrogpenized females.

Adenocarcinoma↗

Growth hormone, insulin, and prolactin secretion in anorexia nervosa and obesity during bromocriptine treatment.

We studied secretion of growth hormone (GH), insulin, and prolactin in eight women with anorexia nervosa and nine women with refractory obesity before and during treatment with bromocriptine, 10 mg/day. In the anorexic patients the raised plasma GH concentrations occurring during an oral glucose tolerance test fell significantly while on bromocriptine treatment, but there was no change in plasma insulin or blood glucose concentrations. In the obese patients, however, plasma GH concentrations remained low during the oral glucose tolerance test, and were not modified by bromocriptine. Blood glucose and plasma insulin concentrations were also unchanged. Plasma GH and plasma 11-hydroxycorticosteroid responses to insulin-induced hypoglycaemia were unaffected. Serum prolactin concentrations which were raised in five anorexic patients and marginally raised in two obese subjects, fell significantly in both groups during treatment. We observed no consistent weight changes in either groups.

Adolescent↗

Effects of bromocriptine on pituitary tumour size.

In a prospective study designed to assess the influence of bromocriptine on pituitary tumour size 12 patients with pituitary tumours, eight of whom had suprasellar extensions, were treated for three months with 20 mg of bromocriptine daily after a gradual increase to this dose. The group comprised eight women and four men, five with prolactin-secreting adenomas, four with acromegaly, two with functionless adenomas, and one with Nelson's syndrome. All five patients with prolactin-secreting adenomas showed a reduction in pituitary tumour size as assessed by computerised tomography and metrizamide cisternography accompanied by a fall in prolactin concentrations and clinical and biochemical improvement in their hypopituitarism. One patient in this group had a visual-field defect before treatment, and this resolved. There was no radiological evidence of reduction in tumour size in the remaining seven patients, though this might refect the fairly short duration of treatment, particularly in view of the ancillary evidence of clinical, biochemical, and visual-field improvement in some of the patients. These results emphasise the potential value of bromocriptine in treating patients with large prolactinomas or recurrences of such tumours after previous chiasmal decompression and conventional external megavoltage irradiation on the pituitary.

Adult↗

Parkinson's disease: an open label trial of pergolide in patients failing bromocriptine therapy.

Sixty-three patients with Parkinson's disease who failed bromocriptine therapy for various reasons were treated in an open-label trial of pergolide. The data were evaluated in a retrospective manner. Forty-six percent had a good response and tolerated the pergolide. A comparison of the outcomes regarding response and toxicity revealed that bromocriptine and pergolide act differently in individual patients. A trial of pergolide in Parkinsonian patients failing bromocriptine therapy may be therapeutically useful.

Adult↗

Effect of bromocriptine and metoclopramide on serum prolactin levels in patients with amyotrophic lateral sclerosis.

Secretion of prolactin in nine patients with amyotrophic lateral sclerosis and in seven healthy men was investigated with the use of metoclopramide stimulation and bromocriptine inhibition tests. Blood serum prolactin concentration was determined in the basal state and 30, 60 and 120 minutes after oral administration of 10 mg metoclopramide or 2.5 mg bromocriptine. A period of 3 days intervened between testing each drug in the same individual. It was shown that basal prolactin levels in amyotrophic lateral sclerosis patients and the controls did not differ significantly, whereas in the metoclopramide stimulation test seven amyotrophic lateral sclerosis patients showed a very exaggerated response. The mean value of maximal prolactin increment was 1609.90% (SD 456) in comparison with the control group 638.3% (SD 89.7) (p less than 0.01). In the bromocriptine inhibition test the mean value of maximal prolactin percentage decrement was 50.4% (SD 6.1) in amyotrophic lateral sclerosis and 66.5% (SD 5.3) in the controls and this difference was statistically insignificant. These data suggest that exaggerated prolactin response to metoclopramide in amyotrophic lateral sclerosis may be a result of a decreased activity of central dopaminergic neurons.

Aged↗

Treating organic abulia with bromocriptine and lisuride: four case studies.

Abulia refers to an impairment of will, or the inability to initiate behaviour and action. There are reports of successful treatment of akinetic mutism, the most severe form of abulia, with bromocriptine. Four case studies are presented describing the successful treatment of abulia at a lesser severity than akinetic mutism with bromocriptine. Abulia was caused by brain damage due to alcohol in two cases, Wilson's disease and basal ganglia infarct in one each. Maximum bromocriptine dose varied from 25-70 mg. All improved considerably. Withdrawal or reduction of medication in three produced deterioration. The prescription of a neuroleptic drug had a similar effect in the fourth. One patient with a previous history developed a depressive relapse and so the drug was withdrawn and lisuride introduced. This produced a similar improvement. These cases highlight the value of identifying the syndrome of organic abulia and suggest that dopamine agonists may have a place in its treatment, though controlled studies are needed.

Adult↗

The Sydney Multicentre Study of Parkinson's disease: a randomised, prospective five year study comparing low dose bromocriptine with low dose levodopa-carbidopa.

149 previously untreated patients with Parkinson's disease were recruited over a three year period and randomly allocated to either low dose levodopa-carbidopa (< or = 600/150 mg/day) or low dose bromocriptine (< or = 30 mg/day). A five year follow up is reported on the 126 patients who completed the dose titration and who have not developed features of atypical Parkinsonism. Levodopa-carbidopa in low dosage adequately controlled symptoms in most patients and delayed the appearance of dyskinesia and end of dose failure for about two years longer than conventional doses. Only a few patients could be managed for more than one year on low dose bromocriptine alone; these patients had mild disease and asymmetric signs. Patients randomised to bromocriptine did not develop dyskinesia or troublesome end of dose failure until levodopa-carbidopa was added. The prevalence of dyskinesia in this group was lower than in patients given levodopa-carbidopa alone. The prevalence of end of dose failure was similar in the two randomisation groups once levodopa was introduced.

Adult↗

Effect of bromocriptine on maturity onset diabetes.

The effect of the dopamine agonist, bromocriptine, and the dopamine antagonist, metoclopramide, on glucose tolerance was examined in maturity onset diabetics and normal subjects. After bromocriptine there was a lowered fasting blood glucose and improved glucose tolerance in the diabetics. The controls showed an initial improvement in glucose tolerance. A reduction in insulin levels and a marked fall in plasma prolactin was observed in all subjects. Growth hormone concentrations were low and unaffected in the diabetics, and there was an inconsistent rise in the normals. After metoclopramide there was some impairment in glucose tolerance in the normal subjects, but this was not significant in the diabetics. There was also a marked prolactin release in all subjects, but no significant effect on insulin or growth hormone. It is concluded that bromocriptine lowers the blood glucose and improves glucose tolerance in maturity onset diabetics. This action may be the result of the lowered prolactin which occurred without a concomitant rise in growth hormone.

Blood Glucose↗

Bromocriptine suppression of dispersed pituitary lactotrophs from estrogen-pretreated rats: a quantitative electron microscopic study.

Dispersed rat lactotrophs were treated with bromocriptine (10(-10) M) for either 30 min or 3 h to investigate its effect on cell morphology using light and electron microscopy and ultrastructural morphometry. After 30 min, lactotrophs treated with bromocriptine exhibited an increase in storage granule size (p less than 0.05). Crinophagy was also evident and a significant increase in lysosome volume density was observed (p less than 0.001). However, no significant change in prolactin content in the media was detected until 3 h of incubation in bromocriptine (p less than 0.05). At this time a nonsignificant decrease in Golgi region volume density was also observed.

Animals↗

Computed tomographic demonstration of the effects of bromocriptine on pituitary microadenoma size.

A group of 17 strictly intrasellar prolactin-secreting pituitary adenomas between 2 and 9 mm in size was examined by computed tomography before and after bromocriptine therapy of 3 months to 1 year duration. These findings were compared with clinical and biological data. Bromocriptine therapy was effective clinically and biologically in 14 of the 17 cases. Of the 15 intrasellar adenomas in nonpregnant patients treated with bromocriptine, six disappeared completely with normalization of the pituitary appearance, five decreased approximately 50% in volume (three showed an increase in density, two a decrease), and four remained unchanged in size (two showed increased density, two showed very low densities).

Adenoma↗

Long-term double masked trial of early treatment with L-dopa plus bromocriptine versus L-dopa alone in Parkinson's disease. Interim results.

The quality and duration of control in two groups of parkinsonian patients under treatment with an L-dopa-based drug alone or L-dopa-based drug which has been partially substituted with bromocriptine are being compared over a 5-year period using a double-blind placebo-controlled study design. The aim is to establish whether early addition of bromocriptine will minimise late L-dopa complications. Results are presented after 1 year. Of 31 patients randomised, 13 were treated with combined L-dopa/bromocriptine and 14 with L-dopa/placebo. 4 patients were withdrawn for various reasons. In both groups any dose adjustments were aimed at maintaining the pre-entry clinical condition. In the group receiving bromocriptine combination therapy, progressive reduction of L-dopa was possible without deterioration of the patients' condition. In patients receiving L-dopa alone, the dose of L-dopa at 12 months was almost similar to that recorded on entry to the study. The total number of patients reporting adverse events in the L-dopa/bromocriptine combination and L-dopa alone groups were 8 and 7, respectively. At the present interim stage of the study it is not possible to compare the incidence of L-dopa long-term complications in either group.

Bromocriptine↗

Effect of bromocriptine mesylate on induced hyperprolactinemia in stabilized psychiatric outpatients undergoing neuroleptic treatment.

Therapeutic doses of phenothiazines increased serum levels of prolactin, resulting in a number of side effects. Bromocriptine, a potent dopamine agonist, appears to effectively reduce the serum prolactin level. In this open pilot study, bromocriptine mesylate (Parlodel, Sandoz) was administered in an escalating dose schedule to 11 stabilized psychiatric outpatients with hyperprolactinemia resulting from thioridazine HCl (Mellaril, Sandoz) treatment. 6 of 9 patients showed decreases. Overall global psychiatric evaluations were unchanged over the course of combined therapy for all but 1 patient, who showed improvement. The trend of decreased prolactin serum levels indicates that bromocriptine mesylate may prove a useful adjunct to reduce the side effects of hyperprolactinemia.

Adolescent↗

The neuroleptic malignant syndrome: occurrence in a 15-year-old boy and recovery with bromocriptine therapy.

The neuroleptic malignant syndrome (NMS) is an idiosyncratic reaction to neuroleptic medication not previously described in the pediatric literature. It is characterized by hyperthermia, extrapyramidal disorders, decreased level of consciousness and autonomic dysfunction. A 15-year-old boy with acute lymphoblastic leukemia developed the NMS after a brief exposure to chlorpromazine and promethazine. He responded favorably to the dopamine agonist bromocriptine. A review of the recent literature suggests bromocriptine as the most efficacious specific therapy. Management of the NMS includes immediate discontinuation of all neuroleptic agents, intense supportive care and prompt institution of bromocriptine therapy.

Adolescent↗

Bromocriptine, lergotrile: the antiparkinsonian efficacy and the interaction with monoaminergic receptors.

The antiparkinsonian activity of bromocriptine and of lergotrile was investigated in monkeys with surgically induced tremor and in parkinsonian patients. Both drugs effectively relieve tremor in experimental monkeys and induce less pronounced abnormal involuntary movements than L-dopa or piribedil. Both drugs were shown to be of therapeutic value in a group of patients with advanced Parkinson's disease who were no longer responsive to levodopa combined with carbidopa. Adverse effects were similar to those observed with levodopa and carbidopa, except that in individual patients abnormal involuntary movements and diurnal oscillations in performance ("on-off" effect) were decreased, while mental changes were increased. The interactions of bromocriptine and of lergotrile with dopamine and alpha-adrenergic receptors were investigated. Both drugs have mixed agonist-antagonist activities with respect to the dopamine receptors; lergotrile has a higher affinity for the agonist site while bromocriptine has a higher affinity for the antagonist site of the receptors. Both drugs effectively displace the binding of the alpha-adrenergic antagonist WB-4101 to cerebral cortex membranes. The mechanisms underlying the antiparkinsonian efficacies of these two drugs were discussed.

Animals↗

Neurochemical and neuropharmacological investigations with four ergot derivatives: bromocriptine, dihydroergotoxine, CF 25-397 and CM 29-712.

Neurochemical and neuropharmacological investigations with four ergot derivatives reveal differential pharmacodynamic effects of these compounds. Bromocriptine and CM 29-712 showed actions typical of postsynaptic dopamine receptor stimulants, in particular in the extrapyramidal system. CM 29-712 proved to be more potent than bromocriptine, with an early onset of action. CF 25-397 and dihydroergotoxine, while not showing all actions typical of central dopamine agonists, appeared to exert some of their effects by means of a stimulation of central serotoninergic sites. In the rat sleep-wakefulness cycles and in reserpine-induced ponto-geniculooccipital waves in the cat, they mimicked the effects of 5-hydroxytryptophan. In the latter test, CF 25-397 proved to be particularly potent. In addition, bromocriptine, dihydroergotoxine and CM 29-712 showed neurochemical effects consistent with central alpha-adrenergic blockade or an enhanced impulse flow in central noradrenergic neurons.

Animals↗