Physiologic disposition of lergotrile

Lergotrile, an ergot alkaloid, has been shown to be effective in treating disorders associated with elevated serum prolactin levels (e.g., galactorrhea‐amenorrhea). Lergotrile has also been found to be a potent dopaminergic agonist and thus to be effective in Parkinson's disease. This study describes the physiologic disposition of lergotrile after administration to human volunteers. N‐14CH3‐lergotrile was rapidly absorbed from the gastrointestinal tract. Lergotrile was detected at low concentrations in plasma when subjects received large doses over extended periods of time. The major portion of radioactivity in plasma was allributed to the presence of circulating metabolites of lergOlrile. Lergotrile metabolites were eliminated in the feces (ca. 60%), urine (ca. 20%), and breath (ca. 7% as 14CO2). A metabolite in feces was identified as 13‐OH‐lergotrile (up 10 30% of the dose). A metabolite in urine was formed by conversion of the C8‐acetonitrile group of lergotrile to a carboxyl group (aboUl /0% of the dose). The presence of 14CO2 in the expired air after administering N‐14C‐methyl‐lergotrile indicated that the drug was N‐demethylated to form norlergotrile.

[1]  H. Rowe,et al.  Physiologic disposition of nabilone, a cannabinol derivative, in man , 1977, Clinical pharmacology and therapeutics.

[2]  Z. Siddik,et al.  1576 – THE METABOLISM of [14C] LSD IN THE RAT , 1977 .

[3]  E. Estey,et al.  LERGOTRILE IN PARKINSON'S DISEASE , 1976, The Lancet.

[4]  Y. Sinha,et al.  A comparison of the effects of CB-154 and lergotrile mesylate on prolactin and growth hormone secretion in mice. , 1976, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[5]  M. Goldstein,et al.  Studies on the antiparkinsonian efficacy of lergotrile , 1975, Neurology.

[6]  J. Clemens,et al.  Inhibition of prolactin secretion by lergotrile mesylate: mechanism of action. , 1975, Acta endocrinologica.

[7]  R. Cleary,et al.  The effect of lergotrile on galactorrhea and gonadotropin secretion. , 1975, The Journal of clinical endocrinology and metabolism.

[8]  P. Murphy,et al.  Metabolism of propionyl erythromycin lauryl sulfate. II. Fate of the lauryl sulfate moiety in the rat and man. , 1975, Drug metabolism and disposition: the biological fate of chemicals.

[9]  J. Clemens,et al.  The inhibitory effect of an ergoline derivative (lergotrile, compound 83636) on prolactin secretion in man. , 1974, The Journal of clinical endocrinology and metabolism.

[10]  J. Clemens,et al.  Inhibition of prolactin secretion by ergolines. , 1974, Endocrinology.

[11]  A. Ridolfo,et al.  Effects of fenoprofen and aspirin on gastrointestinal microbleeding in man , 1973, Clinical pharmacology and therapeutics.

[12]  K. Fuxe,et al.  Tremor and Involuntary Movements in Monkeys: Effect of L-Dopa and of a Dopamine Receptor Stimulating Agent , 1973, Science.

[13]  R. Wolen,et al.  Physiological disposition of fenoprofen in man. 3. Metabolism and protein binding of fenoprofen. , 1972, The Journal of pharmacology and experimental therapeutics.

[14]  J. Axelrod,et al.  The disposition and metabolism of tryptamine and the in vivo formation of 6-hydroxytryptamine in the rabbit. , 1971, The Journal of pharmacology and experimental therapeutics.

[15]  S. Udenfriend,et al.  Microsomal hydroxylation of tryptamine, indoleacetic acid and related compounds, to 6-hydroxy derivatives. , 1962, Biochimica et biophysica acta.

[16]  E. Evarts,et al.  THE DISTRIBUTION AND METABOLISM OF LYSERGIC ACID DIETHYLAMIDE , 1957, Annals of the New York Academy of Sciences.

[17]  E. Boyland.  Detoxication Mechanisms , 1948, Nature.