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Mesulergine, a new dopamine agonist: Effects on anterior pituitary function and kinetics
Author(s) -
Borges Joao L C,
Schran Horst F,
Evans William S,
Rogol Alan D,
Kaiser Donald L,
MacLeod Robert M,
Boyett R Lance,
Elton Richard L,
Thorner Michael O
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.242
Subject(s) - bromocriptine , medicine , endocrinology , prolactin , thyrotropin releasing hormone , dopamine agonist , chemistry , agonist , hormone , receptor
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. (R 2 = 0.27) and the 8 P.M. to 9 A.M (day 2; R 2 = 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. Analysis of mesulergine plasma levels revealed that both AUC 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. Clinical Pharmacology and Therapeutics (1984) 36, 696–703; doi: 10.1038/clpt.1984.242