dihydroergotoxine and Adenoma

Topics: Adenoma; Adrenocorticotropic Hormone; Bromocriptine; Dihydroergotoxine; Dopamine; Drug Administration Schedule; Ergolines; Growth Hormone; Levodopa; Lisuride; Metergoline; Methysergide; Pergolide; Pituitary Neoplasms; Prolactin; Tomography, X-Ray Computed

Although it is well known that bromocriptine (BC) is effective in the treatment of functioning pituitary adenoma, this agent sometimes causes severe gastrointestinal side effects. In this study, dihydroergotoxine mesylate (EX), which is composed of ergot alkaloids and is similar to BC, was administered to 11 patients with functioning pituitary adenomas who could not tolerate the adverse effects of BC. Three patients (27%) showed clinical improvement with EX treatment alone (1 to 6 mg/day). In another patient, computed tomography demonstrated tumor shrinkage. The remaining seven patients experienced adverse effects while taking EX. These results indicate that EX is a useful alternative to BC in the treatment of functioning pituitary adenoma, particularly in patients who cannot tolerate the side effects of BC. Moreover, pretreatment with EX appears to reduce the incidence of side effects of BC.

Topics: Adenoma; Adult; Aged; Antineoplastic Agents; Dihydroergotoxine; Drug Evaluation; Drug Tolerance; Female; Growth Hormone; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Prolactinoma

One tenable hypothesis for the etiology of the development of prolactin-secreting adenomas is that a decrease in inhibitory dopaminergic regulation leads to increased lactotroph proliferation. Dopamine receptors have been repeatedly characterized on prolactin-secreting adenomas using labelled antagonists as ligands; however, no data are available on characterization of the receptor with a dopaminergic agonist. An agonist was utilized as the radioligand in the present study to permit the direct comparison of the pharmacological characteristics of the binding site with the biological response, the inhibition of prolactin secretion. This comparison has never been reported in tissues from the same species. Binding of the dopamine agonist and alpha-adrenergic antagonist [3H]-dihydroergocryptine ([3H]-DHE) to particulate fractions of surgically resected human prolactin-secreting adenomas was high affinity, monophasic, and saturable. Careful characterization of the [3H]-DHE binding by competitions with a large number of dopaminergic and alpha-adrenergic agents revealed the presence of both dopaminergic and alpha-adrenergic binding sites. The presence of a saturable, high affinity alpha-adrenergic binding site was confirmed with the specific alpha-adrenergic antagonist [3H]-WB4101 as a radioligand. Although the rank order of potency for dopaminergic compounds to compete for [3H]-DHE binding was consistent with an interaction with a dopamine receptor, the inhibitory constants (Ki) calculated from the competitions were higher than expected at an anterior pituitary dopamine receptor. This appeared to be due to the lower affinity of these agents at the alpha-adrenergic sites. The observed potency of dopaminergic compounds was inversely related to the number of alpha-adrenergic sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenoma; Adolescent; Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Adult; Binding, Competitive; Dihydroergotoxine; Dioxanes; Dopamine; Dopamine Antagonists; Female; Humans; Male; Middle Aged; Pituitary Neoplasms; Prolactin; Receptors, Adrenergic, alpha; Receptors, Dopamine

The endocrine effects of a relatively potent dopaminergic agent, dihydroergokryptine, have been studied in normal subjects, and in hyperprolactinaemic and acromegalic patients. A single 6 mg oral dose of the drug caused a marked, long lasting fall in prolactin (PRL) plasma levels in healthy subjects, in hyperprolactinaemic patients and in normoprolactinaemic acromegalics. Growth hormone (GH) levels decreased in 1-DOPA - responder, acromegalic patients, but dihydroergokryptine did not affect GH levels in normal volunteers or in 1-DOPA non-responder, acromegalic patients. The PRL- and GH- lowering activity of 6 mg dihydroergokryptine was significantly greater than that of 6 mg dihydroergocristine, and was similar to that of an oral dose of 500 mg 1-DOPA.

Topics: Acromegaly; Adenoma; Adult; Aged; Dihydroergotoxine; Female; Growth Hormone; Humans; Levodopa; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin; Receptors, Dopamine; Time Factors

Topics: Acromegaly; Adenoma; Adolescent; Adult; Amenorrhea; Dihydroergotoxine; Dopamine; Female; Growth Hormone; Humans; Levodopa; Male; Middle Aged; Nomifensine; Pituitary Gland; Pituitary Neoplasms; Prolactin

Topics: Adenoma; Adult; Apomorphine; Bromocriptine; Cells, Cultured; Dihydroergotoxine; Dopamine; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Prolactin