Mesulergine, a new dopamine agonist: Effects on anterior pituitary function and kinetics

Abstract

We investigated the effects of single doses of mesulergine on basal and thyrotropin-releasing hormone (TRH)-stimulated serum levels of several anterior pituitary hormones in healthy men and defined its kinetics. We also compared the effects on serum prolactin (PRL) levels of three doses (0.1, 0.35, and 0.5 mg) of mesulergine to those in response to 2.5 mg bromocriptine. Secretory rates of PRL before the first 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 10 A.M. and 1 P.M. Bromocriptine inhibited TRH-stimulated PRL secretion at 10 A.M. and 8 P.M. When analyzed as the 8 A.M. to 8 P.M. and the 8 P.M. to 9 A.M. (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 8 A.M. to 8 P.M. (R2 = 0.27) and the 8 P.M. to 9 A.M. (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 follicle-stimulating hormone were changed by 0.1 or 0.35 mg mesulergine.(ABSTRACT TRUNCATED AT 250 WORDS)

Cortisol as an indicator of dopaminergic effects on nicotine craving

“…The lack of an overall cortisol response to the two dopaminergic substances is in line with several reports in the literature (Krause et al, 1990;Borges et al, 1984;Sowers and Beck, 1984;Koizumi et al, 1985;Delitala et al, 1979;Verhelst et al, 1991;Hagan and Brooks, 1996;Grunder et al, 1995;Roy et al, 1986). However, the results demonstrated that most subjects are susceptible to a dopaminergic challenge but interestingly, half of them only responded to either the agonist or the antagonist and 8 of 30 to both drugs (Table 1).…”

“…Salokangas et al, 2000) also elicits cortisol responses (Field et al, 1994) which may be DA mediated. In healthy subjects, Moro et al (1997) reported a significant cortisol increase after administration of the DA antagonist metoclopramide, whereas unchanged cortisol levels were observed after application of the partial dopamine agonist, terguride (Krause et al, 1990), the DA agonists bromocriptine (Borges et al, 1984;Sowers and Beck, 1984) or lisuride (Koizumi et al, 1985;Delitala et al, 1979). Also other studies performed in clinical settings yielded negative results of DA agonists or DA antagonists on cortisol secretion (Verhelst et al, 1991;Hagan and Brooks, 1996;Grunder et al, 1995;Roy et al, 1986) and no hyperor hypocortisolism after treatment with DA related substances has been reported in patients.…”

Treatment of human hyperprolactinaemia with a new dopamine agonist: CU 32085 (mesulergin)

“…However, we think that this is unlikely since Prl levels always returned to their initial levels in all patients before they were given CU 32085. Furthermore, our data are in agree¬ ment with observations by others that in normal men, 0.5 mg is the minimal dosage for 24 h suppression of Prl (Borges et al 1984). This longlasting action of CU 32085 allowed most of our patients to maintain their Prl within the normal range with a single administration of 0.5 mg or 1 mg/day.…”

Mesulergine: A Review

“…The t 1/2 of mesulergine distribution phase is 2 h and of the elimination phase 10 h, while the t 1/2 of bromocriptine is 4 to 5 h (8). The C max of mesulergine and its metabolites (4 to 5 ng/mL/mg) considerably exceeds that of bromocriptine (approximately 0.2 ng/mL/mg), suggesting the kinetic equivalence of 0.1 mg mesulergine and 2.5 mg bromocriptine (8,19).…”

“…Derivatives of ergot alkaloids, bromocriptine, lisuride, and pergolide have been used in the treatment of pituitary adenomas (8,19,43,57) (Table 1). In the case of prolactinomas, mesulergine (at relatively low doses up to 1.5 mg/d) has been reported to normalize prolactin levels in nearly 67% of female patients.…”