Acute Administration Of Bromocriptine Research Articles

Bromocriptine Effect in Spontaneous Motor Activity Using Albino Mice

Bromocriptine is a potent agonist at the D2 receptor. The aim of this study is to investigate the bromocriptine effect in spontaneous motor activity, using variable doses with acute and subacute administration and variable onset of measurement using albino mice. Acute intraperitonealadministration of bromocriptine using doses of 0.625, 2.5, 5, and 10mg/kg and thecontrol group administration of 1% tween 80(n=7) were used. Spontaneous motor activity was scored after 30 and 60min of administration. Subacute administration is as follows:group1was administered 1% tween 80asa control and group2 was administered 10mg/kg bromocriptine. Spontaneous motor activity was scored using an open field test. Acute administration of bromocriptine after 30min (0.625 and 2.5mg/kg) did not show any significant changes in spontaneous motor activity while 5 and 10mg/kg produced a significant decrease. Acute administration of bromocriptine after 60min produced a significant decrease in spontaneous motor activity, with 0.625, 2.5, 5, and 10mg/kgdoses. Subacute administration of bromocriptine significantly increased spontaneous motor activity,compared to control. It is concluded that acute administration of bromocriptine at 30min decreased spontaneous motor activity, only with higher doses while its acute administration after 60min decreased spontaneous motor activity,with all doses (0.625, 2.5, 5, and 10mg/kg). As subacute administration increased spontaneous motor activity,these findings conclude that bromocriptine which produced its effect in spontaneous motor activityis time and dose dependence.

Neuroendocrine correlates of antisocial personality disorder in abstinent heroin-dependent subjects

The function of the central alpha-adrenergic, serotoninergic and dopaminergic systems was investigated in 30 heroin-dependent subjects, 6 - 8 weeks after detoxification and in 22 psychophysically healthy controls (group C). Twelve heroin-dependent subjects with antisocial personality disorder (ASPD) (group A), 18 heroin-dependent subjects without other Axis I and II pathologies (group B) were included among abstinent substance abusers. The norepinephrine (NE) function was evaluated by the GH responses to acute stimulation with clonidine (clon); the serotonin (5-HT) function by the PRL and cortisol (CORT) responses to acute stimulation with d-fenfluramine (d-fen) and the dopamine (DA) function was investigated by growth hormone (GH) and prolactin (PRL) responses to acute administration of bromocriptine (brom). Alpha-adrenergic sensitivity, as measured by the GH-clon test, was found significantly reduced in A subjects (ASPD), in comparison with B subjects and controls. PRL and CORT responses to d-fen were significantly blunted both in A and B subjects, in comparison with control subjects. DA receptors sensitivity seems to be reduced significantly in ASPD (A subjects); in contrast, heroin addicts without open psychiatric co-morbidity showed unimpaired responses to brom challenge; a significantly lower GH response to brom and a lack of PRL suppression in ASPD subjects could express D2 postsynaptic receptor hyposensitivity possibly related to DA gene variants associated to co-morbid disorder. In sum, the study of central monoamine function revealed an alteration of the 5-HT system in all detoxified heroin-dependent subjects. A significant reduction of alpha-adrenergic receptors sensitivity and the hyposensitivity of postsynaptic DA receptors in ASPD subjects suggest once again that specific biological correlates of psychiatric co-morbidity may characterize substance abusers subtypes.

Effects of D 2 dopamine receptor agonist and antagonist on brain activity in the rat assessed by functional magnetic resonance imaging

The effects of D 2 dopamine receptor agonist, bromocriptine (BROMO), and antagonist, haloperidol (HPD), on brain activity were investigated in rats by functional magnetic resonance imaging. T2 *-weighted signal intensity was increased in the hypothalamus at 120 min after acute administration of BROMO, and in the ventral posterior and dorsomedial nuclei of the thalamus from 30 to 120 min. In contrast, the signal intensity was decreased in the caudate–putamen at 30 min after acute administration of HPD, in the hypothalamus from 30 to 60 min, and in the perirhinal cortex at 30 min. After chronic (2 weeks) HPD treatment, acute administration of HPD decreased signal intensity in the caudate–putamen at 60 min, in the hypothalamus at 30 min, the perirhinal cortex from 2 to 120 min, the dorsomedial and ventral posterior nuclei of the thalamus from 2 to 120 min, and the medial nucleus of the amygdala from 60 to 120 min. These results suggest that (1) the D 2 receptor agonist increased the activity of the thalamic nuclei and the hypothalamus, while the D 2 receptor antagonist suppressed brain activity in the regions where D 2 receptors were present, (2) the suppression of brain activity in the thalamic nuclei and the perirhinal cortex by acute HPD administration was enhanced by chronic HPD treatment, and (3) the effects of antipsychotic drugs on the thalamus, amygdala, and perirhinal cortex may be related to their therapeutic efficacy, since clinical improvement in schizophrenic patients appears several days after the start of HPD treatment.

Prolactin response to bromocriptine in flunarizine-treated migrainous women.

Flunarizine, a calcium channel blocker, is widely used in migraine prophylaxis. Although an antidopaminergic effect has been suggested for this drug, it is unclear whether the antimigraine action of flunarizine involves the dopaminergic system. We studied the inhibitory response of prolactin to acute administration of bromocriptine, a D2 dopamine receptor agonist, before and after 1 month of treatment with flunarizine in migrainous women. Flunarizine treatment increased basal prolactin levels, but it did not reduce the inhibitory response of prolactin to acute bromocriptine administration. These findings do not support the hypothesis that flunarizine acts as a direct antagonist at the D2 dopamine receptor.

Usefulness of thyrotropin-releasing hormone test, SMS 201-995, and bromocriptine in the diagnosis and treatment of gonadotropin-secreting pituitary adenomas.

Five patients with gonadotropin-secreting pituitary adenomas were studied. The utility of gonadotropin response to TRH stimulation in the diagnosis and follow-up of these tumors was evaluated, as well as the effects of somatostatin analogue SMS 201-995 and bromocriptine on gonadotropin release. Three patients had FSH and LH secreting adenomas while the other two tumors secreted FSH and alpha-subunit. Transsphenoidal resection of the pituitary adenomas were performed in all patients. Following preoperative TRH administration (400 micrograms i.v.), marked increases were observed in FSH levels in two cases, in LH levels in three and in alpha-subunit in one. The FSH and LH responses to t.his stimulus persisted in the same patients after surgery. Following acute bromocriptine administration (5 mg orally), FSH was reduced in all cases by 19% to 46%, LH in three cases by 50-67% and alpha-subunit in one by 33%. In patient no. 5, with persistent high FSH levels in the immediate postoperative period, long-term bromocriptine treatment was administered (15 mg/d orally), resulting in normalization of FSH levels 6 months later, although the size of the tumor was not reduced. After acute SMS 201-995 administration (100 micrograms sc) FSH decreased in two cases by 38% and 76%, LH in three by 30-56% and alpha-subunit in one by 20%. We conclude that gonadotropin response to TRH stimulation is useful in the diagnosis and follow-up of patients with gonadotroph adenoma. Bromocriptine and SMS 201-995 may be effective as coadjuvant treatment following surgery and radiotherapy in these patients, although long-term studies will be necessary to confirm these proposals.

Acute administration of bromocriptine abolishes the hyperprolactinemic response induced by submaximal exercise in man.

The effective control of hypophysial prolactin (PRL) secretion with a pharmacological agent is a prerequisite for the investigation of the role of hyperprolactinemia observed during exercise. Using bromocriptine, a potent inhibitor of PRL secretion, this study established the proper experimental conditions whereby any significant increase in plasma PRL level can be prevented and basal circulating levels maintained during physical exercise. On three occasions at weekly intervals, 15 male adults, separated into two groups, exercised on an ergocycle (40 min at 65% VO2max) either 1 or 3 h after ingesting either placebo or 1.25 or 2.50 mg of bromocriptine mesylate (Parlodel; Sandoz Canada Inc., Dorval, Qué.). Under all conditions, the plasma PRL elevation observed during exercise after placebo was prevented by the administration of bromocriptine. Resting plasma PRL levels were maintained when exercise was performed 1 h after bromocriptine ingestion, but were significantly reduced when exercise was performed 3 h after administration of either bromocriptine dosages. Considering the primary and secondary effects observed, 1.25 mg of bromocriptine administered 1 h before exercise provides suitable experimental conditions to investigate the role of the increase in plasma PRL during physical exercise.

A Double Blind Controlled Study of the Hormonal and Clinical Effects of Bromocriptine in the Polycystic Ovary Syndrome

Previous studies on the efficacy of bromocriptine for the treatment of patients with the polycystic ovary syndrome failed to include control groups. This study, therefore, was undertaken to determine the clinical and endocrine effects of bromocriptine and a placebo (given in a random double blind fashion) in 55 patients with PCOS. The plasma levels of estrone, estradiol, testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, 17-hydroxyprogesterone, and serum PRL and gonadotropins (LH and FSH) were measured before treatment. In addition the serum PRL response to TRH and the serum LH and FSH response to GnRH were determined. The effects of acute administration of bromocriptine (2 X 2.5 mg at 12-h intervals) on serum gonadotropins and their response to GnRH were studied to explore the possibility that this test might predict the response to chronic bromocriptine treatment. Bromocriptine then was given at an initial dose of 1.25 mg twice daily. If no clinical improvement occurred 2.5 mg were given twice daily for at least 6 months. Hormonal measurements and dynamic tests were repeated after 3 and 6 months of therapy. The endocrine profile of the two groups was not different before treatment. The clinical results were not better in the treatment group than in the placebo-treated patients: therapy was successful (restoration of ovulatory cycles of less than 35 days duration) in 12 of 28 patients taking bromocriptine vs. 8 of 27 taking placebo. Slight improvement (1 or 2 ovulations) occurred in 3 of 28 vs. 3 of 27, and failure (no clinical change) in 13 of 28 taking bromocriptine vs. 16 of 27 taking placebo, respectively. Serum PRL fell significantly in the bromocriptine group, and there was a significant fall in the serum LH response to GnRH in both groups. No hormonal measurement or response predicted the clinical response to treatment. The only significant effect of chronic bromocriptine therapy (5 mg/day) in patients with the polycystic ovary syndrome was to lower the serum PRL concentration.

Relationship between somatomedin-C and growth hormone levels in acromegaly: basal and dynamic evaluation.

The relationship between basal and stimulated plasma GH and somatomedin-C (SmC) levels in acromegalic patients was evaluated. The basal plasma SmC levels of 66 patients were significantly correlated (P less than 0.01) with mean daily plasma GH levels, but not with the percent GH increase after GH-releasing hormone or TRH or the GH decrease after acute bromocriptine administration. Bromocriptine (7.5-15 mg/day) administration for 9.2 +/- 0.9 (+/- SD) months in 20 patients significantly (P less than 0.05) decreased GH levels. SmC decreased significantly [from 9.8 +/- 1.9 to 5.1 +/- 0.7 U/ml (mean +/- SE)] only in the 10 patients who had the more marked GH inhibition. The administration of a somatostatin analog, SMS 201-995 (100 micrograms twice daily), to 12 patients for 16 weeks significantly decreased plasma GH and SmC levels beginning on the second day of therapy; normal SmC levels were achieved in 5 of 12 patients. Pituitary adenomectomy resulted in normal GH and SmC levels in 10 of 12 and 8 of 12 patients, respectively. Our data indicate an overall dependency of plasma SmC levels on plasma GH levels in acromegaly, although similar GH levels may have differing somatomedin-stimulating activities. A derangement in the feedback mechanisms controlling GH secretion is indicated by the failure of elevated SmC levels to influence the GH responsiveness to releasing hormones. In evaluating pharmacological or surgical treatments of acromegaly, a single plasma SmC value can reliably replace several plasma GH determinations.

The effects of bromocriptine on anovulatory patients with high LH and euprolactinemia

It is well known that an acute administration of Bromocriptine (dopamine agonist) suppresses the serum LH level either in normal women or in women with polycystic ovary syndrome, in whom the serum LH level is elevated. The present study was carried out to examine the effectiveness of Bromocriptine on anovulatory women with a high LH level (serum LH greater than 30 mIU/ml). Bromocriptine was administered for 3 months, 5 mg daily, to 9 anovulatory women with euprolactinemia (serum PRL less than 25 ng/ml). Ovulation was observed by their BBT charts. Before and after the treatment of Bromocriptine, FSH, LH and PRL secreting capacities were tested by LHRH and TRH injection. Also, estrone, estradiol and testosterone levels were measured before and after the Bromocriptine administration. Resting levels of LH, FSH and PRL were 45.4 +/- 11.0 mIU/ml, 11.4 +/- 3.0 mIU/ml, and 14.3 +/- 4.7 ng/ml (M +/- SD), respectively, before the treatment. As a result of the treatment, the LH level was markedly decreased to 27.3 +/- 14.5 (M +/- SD, P less than 0.05), and PRL decreased to 3.76 +/- 4.2 ng/ml (M +/- SD, P less than 0.005). On the other hand, FSH did not show a marked change. The responsiveness of LH to LHRH before the treatment showed a marked increase, which was suppressed by Bromocriptine. However, FSH showed no change. The responsiveness of PRL to TRH was suppressed by Bromocriptine. Serum estrone, estradiol and testosterone levels before the treatment were 115.5 +/- 76.7 pg/ml, 93.7 +/- 61.0 pg/ml and 0.809 +/- 0.209 ng/ml (M +/- SD), respectively, which showed no significant change after the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)