title: Mechanism of action and tolerance of mesulergine.
abstract: The tolerance and prolactin (PRL) release-inhibiting action of the 8 alpha-aminoergoline, mesurlergine, were investigated. In a blind crossover study in six subjects with hyperprolactinemia, 0.5 mg mesulergine induced fewer side effects than did 2.5 mg bromocriptine, while the PRL release-inhibiting effect of the two was of the same order. Six different subjects with suspected PRL-secreting pituitary adenomas who (repeatedly) had to discontinue bromocriptine because of nausea, vomiting, or symptoms of orthostatic hypotension were treated for 20 mo with mesulergine (1 to 2 mg/day). Mesulergine did not induce side effects and its actions resembled those of bromocriptine. Mesulergine induced cessation of galactorrhea and resumption of normal menstrual cycles in five subjects, while in one subject an insufficient luteal phase persisted. No abnormalities in routine blood parameter estimations were observed. In two of three subjects there was shrinkage of a pituitary tumor after 12 to 15 mo on mesulergine. Mesulergine did not directly inhibit PRL release by cultured normal rat pituitary cells and human prolactinoma cells and it antagonized the action of dopamine in a dose-dependent manner. This suggests that the dopaminergic action is carried out by a metabolite of mesulergine, while the parent drug probably prevents the well-known side effects of dopamine-agonistic drugs by its dopamine receptor blocking activity. Because of its acceptability, mesulergine might be important in the treatment of hyperprolactinemia and perhaps also of acromegaly and Parkinson's disease.
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000378:metabolism; D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001971:Bromocriptine / Q000009:adverse effects / Q000627:therapeutic use*; D002478:Cells, Cultured; D018492:Dopamine Antagonists; D004341:Drug Evaluation; D004873:Ergolines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008598:Menstruation / Q000187:drug effects; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011388:Prolactin / Q000097:blood* / Q000378:metabolism; D011863:Radioimmunoassay; D011897:Random Allocation; D051381:Rats
chemical_list: D018492:Dopamine Antagonists; D004873:Ergolines; D001971:Bromocriptine; D011388:Prolactin; C031649:mesulergine