Hormonal effects of CV 205-502, a novel octahydrobenzo [g] quinoline with potent dopamine agonist properties

Détails

ID Serval
serval:BIB_45D0747DF45D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hormonal effects of CV 205-502, a novel octahydrobenzo [g] quinoline with potent dopamine agonist properties
Périodique
Life Sciences
Auteur(s)
Gaillard  R. C., Brownell  J.
ISSN
0024-3205 (Print)
Statut éditorial
Publié
Date de publication
1988
Volume
43
Numéro
17
Pages
1355-62
Notes
Clinical Trial
Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Résumé
Following the success of ergot alkaloids and their synthetic derivatives in treating a variety of pathophysiological disturbances, efforts have been concentrated on the synthesis of new derivatives and partial structures with the aim of dissecting out a specifically dopaminomimetic pharmacophore. Accordingly CV 205-502, a structure which superposes the linear benzo [g] quinoline segment of apomorphine on the substituted pyrrolo [3,4- g] quinoline moiety of the ergolines was designed. This study was performed in normal young volunteers to investigate the effect of single oral doses of CV 205-502 on plasma prolactin levels and on other endocrine parameters (GH, LH, FSH, TSH and cortisol) as well as on tolerability. 10 volunteers participated in a dose-ranging study. They received single oral doses of 0.01 to 0.09 mg CV 205-502, in order to assess the prolactin suppressant action. 6 volunteers were given a dose of 0.06 mg CV 205-502 in order to determine the endocrine profile of the compound. The duration of action of 0.06 mg CV 205-502 was investigated in 6 subjects by measuring plasma PRL and GH levels for 48 h. The results show strong dose-dependent suppression of PRL appearing following doses between 0.04 and 0.09 mg of CV 205-502. PRL was markedly suppressed for more than 24h. and the peaks of the normal sleep profile were abolished. Intermittent transient GH increases occurred during the first 6 hours; sleep profiles were normal. Compared with placebo values, no changes were seen in the levels of any other hormone except TSH, which decreased. Tolerability was good and no drug attributable changes in safety measures occurred. This study demonstrates that CV 205-502 is a potent and long acting PRL suppressant compound and suggest that this novel octahydrobenzo [g] quinoline will prove to be a therapeutically useful dopaminomimetic compound.
Mots-clé
Adult Aminoquinolines/adverse effects/pharmacokinetics/*pharmacology Dopamine Agents/adverse effects/pharmacokinetics/*pharmacology Double-Blind Method Drug Tolerance Follicle Stimulating Hormone/blood Growth Hormone/blood Humans Luteinizing Hormone/blood Male Pituitary Hormones, Anterior/*blood Prolactin/*blood Sleep/drug effects Thyrotropin/blood
Pubmed
Web of science
Création de la notice
15/02/2008 17:57
Dernière modification de la notice
03/03/2018 16:46
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