dironyl and Hyperprolactinemia

In a randomized double-blind study, 20 parkinsonian patients (suffering from the disease for 2-18 years), chronically treated with levodopa (500-750 mg/day for 0.5-12 years), received terguride (1 mg b.i.d.) or placebo for 4 weeks. Growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone (TSH), and insulin-like growth factor (IGF-I) secretions were studied before and after the morning dose of levodopa (250 mg p.o.), both before and at the end of study period. At the beginning of the study, basal hormonal levels were within normal limits, and levodopa administration induced a significant suppression in PRL and TSH levels (both p < 0.01)) and a significant increase in GH (p < 0.01). The same results were observed at the end of the study period in the placebo group. Addition of terguride induced a significant suppression in basal PRL levels (p < 0.01), whereas levodopa-induced hormonal changes were unaffected. These data suggest that the hypothalamic dopaminergic function that controls anterior pituitary hormones is preserved in parkinsonian patients, regardless of both the duration of the disease and the long-term treatment with levodopa. The strong additional prolactin-lowering effect of terguride indicates long-lasting dopaminergic effects, as is already known from hyperprolactinemic conditions. The dopaminergic effects of levodopa on TSH, GH, and IGF-I secretion were unchanged by terguride treatment. The anti-dopaminergic effects of terguride observed in the motor system in animal studies, as well as in levodopa-induced dyskinesias in parkinsonian patients, could not be observed in the case of the dopaminergic control of anterior pituitary hormones under the conditions of this study.

Topics: Aged; Antiparkinson Agents; Dopamine Agonists; Double-Blind Method; Female; Humans; Hyperprolactinemia; Levodopa; Lisuride; Male; Middle Aged; Parkinson Disease; Pituitary Function Tests; Pituitary Gland, Anterior; Pituitary Hormones, Anterior

Hyperprolactinemia can successfully be treated by dopaminagonists such as bromocriptin or lisuride. About 10% of patients complain about side effects like orthostatic hypotension, nausea or vomiting, which may lead to discontinuation of treatment. We therefore conducted a study using terguride--a new dopaminagonist--in 5 patients with hyperprolactinemia and intolerable side effects under conventional treatment. Terguride is the transdihydroderivative of lisuride (Dopergin). We treated 5 patients, 2 men with macroprolactinoma and 3 women with microprolactinoma with terguride. The mean duration of treatment was 15.6 months (7-37 months). Patients were treated with up to 5 mg terguride daily. All 5 patients had a marked initial decrease of elevated prolactin levels 8 h after administration of 0.25 mg terguride orally. Three patients became normoprolactinemic after sufficient increase of the dose of terguride, 2 female patients with a microprolactinoma got eumenorrhoeic thereafter. The treatment with terguride was tolerated without side effects by all patients. There were no significant changes of the examined parameters of clinical chemistry nor the other pituitary hormones. Results of cranial computertomography did not change in 4 patients, one patient had tumor progression. Tergurid as a dopaminagonist is an effective inhibitor of prolactin with little side effects and thus a useful drug in the treatment of hyperprolactinemia.

Topics: Adult; Clinical Trials as Topic; Dose-Response Relationship, Drug; Ergolines; Female; Follow-Up Studies; Humans; Hyperprolactinemia; Lisuride; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma; Prospective Studies

Terguride has been widely used for the treatment of hyperprolactinemia via partial agonistic action on dopamine D2 receptors in the pituitary. The present study analyzed retrospectively the dopamine D2 receptor binding occupancy (phi) of terguride. The average phi value was estimated to be 14.1% after oral administration of the average/standard therapeutic dose of terguride. Taking the intrinsic activity (alpha) into consideration, the value of alpha. phi was 2.33%. These results suggest that the antihyperprolactinemic effect of terguride was elicited despite the low receptor occupancy. Furthermore, we developed a pharmacokinetic/pharmacodynamic model for ascertaining the serum prolactin-lowering effect of terguride, considering both the reversible binding to D2 receptors and the effect on the increase rate in the prolactin level. The developed model fit well with the actual data. Although this model could be improved, it could explain the long duration of the antihyperprolactinemic activity of terguride and might be useful for designing its rational dosage regimen.

Topics: Administration, Oral; Drug Administration Schedule; Humans; Hyperprolactinemia; Lisuride; Models, Biological; Pituitary Gland; Receptors, Dopamine D2; Retrospective Studies

BAM-1120, an ergoline derivative, has been found to display a relatively high affinity for dopamine D2-like receptor subtypes in a preliminary binding study. This study investigated whether BAM-1120 acts as a dopamine receptor agonist on prolactin-secreting and motor functions. BAM-1120 suppressed hyperprolactinemia induced by pretreatment with reserpine or estradiol in female rats. Furthermore, BAM-1120 was able to shrink a prolactin-secreting pituitary tumor (prolactinoma) in the estradiol-treated female rats. BAM-1120 induced rotations contralateral to the lesion side in rats with unilateral 6-hydroxydopamine-induced lesions of nigrostriatal dopamine pathway at a dose that was at least 30-fold higher than that required for the inhibition of prolactin secretion. These findings suggest that BAM-1120 is characterized as a putative dopamine D2-like receptor agonist that possesses a preference of inhibiting prolactin secretion over activating motor behaviors.

Topics: Animals; Bromocriptine; Dopamine; Dopamine Agents; Dopamine Agonists; Ergolines; Estradiol; Female; Hyperprolactinemia; Lisuride; Male; Rats; Rats, Wistar; Reserpine; Rotation; Stereotyped Behavior; Sympathectomy, Chemical; Sympatholytics

Plasma prolactin was measured in genetically hypertensive obese Koletsky rats, in their lean siblings and in normotensive rats of Wistar strain. Lean as well as obese females show hyperprolactinemia. The males of Wistar strain as well as obese rats and their siblings show comparable prolactinemia except lean males which show higher level than Wistar males. Sex dependence of prolactinemia is missing in the rats of Wistar strain. Long lasting terguride treatment decreases prolactinemia in obese as well as lean rats of both sexes. The drug showed decreased prolactinemia in the males of Wistar strain. When the group of rats are considered in correlation computation positive correlation can be documented between total plasma cholesterol and plasma prolactin. In obese females positive correlation was found between plasma insulin and plasma prolactin.

Topics: Animals; Body Weight; Dopamine Agonists; Female; Hyperprolactinemia; Hypertension; Insulin; Lipids; Lisuride; Male; Obesity; Prolactin; Rats; Rats, Inbred SHR; Rats, Wistar

Terguride, a derivative of the ergot alkaloid, was characterized as a new anti-hyperprolactinemic agent in rats and dogs in comparison with bromocriptine. Terguride was found to bind selectively to the pituitary dopamine D2-receptors with a high affinity (Kd = 0.39 nM). In reserpinized rats, terguride at 0.03 mg/kg, p.o. significantly reduced the serum prolactin (PRL) level. The PRL lowering effect and the effective dose were longer lasting and about 30 times lower than those of bromocriptine, respectively. In rats bearing estrogen-induced pituitary prolactinoma, chronic terguride induced shrinkage of the prolactinoma as well as reduction of the high serum PRL level. In lactating rats, terguride (1.0 mg/kg, s.c.) reduced milk production in the mammary gland, whereas bromocriptine showed no significant effect up to 10 mg/kg, s.c. Terguride (10 mg/kg, p.o.) did not induce any stereotypy and hypermotility in reserpinized rats, while bromocriptine induced both stereotypy and hypermotility significantly at 10 mg/kg, p.o. In dogs, terguride, like bromocriptine, reduced the serum PRL level, but did not affect the serum levels of growth hormone and luteinizing hormone. In dogs, bromocriptine induced both emesis and PRL-lowering at almost the same dose, whereas emesis-inducing doses of terguride were about 100 times higher than the PRL-lowering dose. These results suggest that terguride as a dopamine D2-agonist is a potent inhibitor of PRL secretion with less neurotropic side effects compared to bromocriptine, and thus a useful drug for the treatment of galactorrhea and hyperprolactinemia including prolactinoma.

Topics: Animals; Bromocriptine; Dogs; Dopamine Agents; Estradiol; Female; Glutathione; Hyperprolactinemia; Lactation; Lisuride; Luteinizing Hormone; Male; Motor Activity; Pituitary Neoplasms; Prolactinoma; Rats; Rats, Wistar; Receptors, Dopamine D2; Reserpine; Stereotyped Behavior; Vomiting

Thirty-two women with ovarian dysfunction due to hyperprolactinemia were treated with a new derivative of lisuride-terguride. Twenty-three patients were treated for infertility. A microadenoma was confirmed in five, and three other patients had had a macroprolactinoma surgically removed. The finding in one of the patients was diagnosed as the syndrome of empty sella. Galactorrhea was present in 18 women. The duration of treatment ranged from 2 to 33 months. The determination of therapeutic dosages was based on individual responses on the prolactin levels within a range from 0.1 to 4.5 mg per day. Increased prolactin levels were successfully normalized in twenty-one treated patients. Regular periods were reappeared in 59% of the women. Thirteen (56%) became pregnant, seven gave birth to healthy babies, two of the patients aborted in the first trimester. Four women are still in later stages of pregnancy. Galactorrhea disappeared in 56% of the patients, being markedly inhibited in the remaining ones. In two cases, microadenoma disappeared after treatment, and in those after surgery the postoperative findings were decreased, in one patients there is no alteration in the pathology. Side effects were seen in 34% of the patients, being mostly mild in nature, and including in most cases nausea, headache and stomach pain. The complaints were transient, receding after prolonged treatment.

Topics: Adolescent; Adult; Female; Humans; Hyperprolactinemia; Lisuride; Prolactin

Topics: Adolescent; Adult; Corpus Luteum; Ergolines; Female; Humans; Hyperprolactinemia; Infertility, Female; Lisuride; Menstruation Disturbances

Terguride, is an 8 - alpha - ergoline derived from lisuride, acts as a partial dopamine (DA) agonist. The effect and tolerance of terguride has been investigated by an acute administration of 0.2 mg p.o. to 8 normal women, 8 patients with hyperprolactinaemia and 8 women with puerperal hyperprolactinaemia. Prolactin (PRL) levels were markedly suppressed in all subjects, with no significant differences between the groups. Treatment for 5 days with terguride 0.4 mg/day or 0.8 mg/day was studied as an inhibitor of lactation. PRL levels were suppressed in a dose-related manner. No untoward side-effects were noted.

Topics: Adult; Dose-Response Relationship, Drug; Ergolines; Female; Humans; Hyperprolactinemia; Lactation; Lisuride; Postpartum Period; Pregnancy; Prolactin; Time Factors

The long term effectiveness and tolerance of terguride, a new ergot derivative, as initial therapy were evaluated in 20 patients with pathological hyperprolactinemia (PHP; group A) and 7 patients with acromegaly. We also studied 10 patients with PHP whose treatment was changed from bromocriptine or lisuride to terguride (group B). Terguride, given for at least 6 months in divided doses ranging from 0.25-1.50 mg/day to group A patients, resulted in normal (11 patients) or markedly reduced plasma PRL levels. Gonadal function was restored in all but 2 patients in this group, and the tumors shrank in 3 of 5 patients with a macroprolactinoma and in 1 of 3 patients with a microprolactinoma. In group B patients, positive effects of the previous treatment on PRL levels, gonadal function, and tumor growth were maintained by terguride. Terguride suppressed plasma GH levels below 50% of baseline in 4 of the 7 acromegalic patients. Two of the 27 patients initially treated with terguride complained of mild nausea and postural hypotension only after the first dose (0.25 mg) of the drug. No patient in group B had any side-effects during terguride, with the exception of 1 patient who was also intolerant to bromocriptine. We conclude that terguride is an effective well tolerated dopaminergic agent in PHP.

Topics: Acromegaly; Adenoma; Adolescent; Adult; Ergolines; Female; Humans; Hyperprolactinemia; Lisuride; Male; Menstruation; Middle Aged; Pituitary Neoplasms

Topics: Acromegaly; Adolescent; Adult; Aged; Ergolines; Female; Humans; Hyperprolactinemia; Lisuride; Male; Middle Aged; Pregnancy

Topics: Acromegaly; Adult; Aged; Ergolines; Female; Growth Hormone; Humans; Hyperprolactinemia; Lisuride; Male; Middle Aged; Prolactin