MESULERGINE, A NEW DOPAMINE AGONIST - EFFECTS ON ANTERIOR-PITUITARY FUNCTION AND KINETICS

The effects of single doses of mesulergine on basal and TRH-stimulated serum levels of several anterior pituitary hormones in healthy men were investigated and its kinetics were defined. The effects on serum prolactin (PRL) levels of 3 doses (0.1, 0.35, and 0.5 mg) of mesulergine to those in response to 2.5 mg bromocriptine were compared. Secretory rates of PRL before the 1st dose of TRH were not affected by any dose of mesulergine or bromocriptine. TRH-stimulated PRL secretion was not altered by 0.1 mg mesulergine but was blunted by both the 0.35- and 0.5-mg doses at 1000 h and 1300 h. Bromocriptine inhibited TRH-stimulated PRL secretion at 1000 h, and 2000 h. When analyzed as the 0800 h to 2000 h and the 2000 h to 0900 h (day 2) intervals, PRL secretion was not changed by 0.1 or 0.35 mg mesulergine but was suppressed during both periods by the 0.5-mg dose. A dose-response relationship was evident, however, between mesulergine and PRL secretion during both the 0800 h to 2000 h (R2 = 0.27) and the 2000 h to 0900 h (day 2; R2 = 0.18) intervals. Bromocriptine lowered PRL secretion during both intervals. Secretory rates of growth hormone during these intervals were not affected by 0.1 mg or 0.35 mg mesulergine but were increased during both intervals by the 0.5-mg dose. Neither the secretory rates of thyrotropin in response to TRH nor those of cortisol, luteinizing hormone, or FSH were changed by 0.1 or 0.35 mg mesulergine. Analysis of mesulergine plasma levels revealed that both AUC [area under the curve] and peak concentrations increased in a linear fashion with increasing doses of mesulergine. Although adverse effects after both mesulergine and bromocriptine included orthostasis, nausea, nasal congestion, and headaches, frequency of orthostatic symptoms and nausea was higher after bromocriptine than after mesulergine. Mesulergine appears to inhibit PRL secretion at doses lower than those of bromocriptine and may be associated with less frequent side effects.