Abstract. CQP 201—403 is a propylergoline derivative with strong dopamine stimulant properties in animals models. It was developed in order to meet the need for a dopamine agonist compound which would offer longer action and improved tolerability. In this study, we tested CQP 201—403 in healthy male volunteers in order to assess its PRL suppression action and other hormonal effects as well as its duration of action and tolerability. Twenty-one volunteers participated in a dose-range study conducted according to a double-blind cross-over design with placebo control. The PRL suppression effect of single oral doses ranging from 0.05 mg to 0.035 mg were investigated. The duration of action of CQP 201—403 was tested in 6 other volunteers receiving a single oral dose of 0.025 mg or placebo. Blood was sampled over 48 h for PRL and GH measurements. An endocrine profile was performed in 6 volunteers receiving either 0.025 mg CQP 201—403 as a single oral dose or placebo. Blood was sampled over 8 h for measuring plasma PRL, GH, LH, FSH, TSH and cortisol. The results show strong dose-dependent PRL suppression (P< 0.001) begining 2 h after ingestion. PRL suppression lasted for more than 24 h and the normal sleep PRL surges were abolished. GH was transiently stimulated during the first few hours; the GH sleep profile was normal. All other hormones were not affected by the administration of CQP 201—403. Tolerability was good and no drug attributable changes in safety measures occurred. This study demonstrated that CQP 201—403 is a potent and long-acting PRL suppression compound in healthy volunteers. Strong PRL suppression and optimal tolerability were achieved with the 0.025 mg dose. This new dopamine agonist promises to be a therapeutically useful dopaminomimetic compound which could probably be prescribed at a once-daily dosage.
R. C. Gaillard and J. Brownell
Paige K. Besch, Katherine A. Brownell, Frank A. Hartman and David J. Watson
Five steroids more polar than cortisol were found in the adrenal vein plasma of experimentally prepared renal hypertensive dogs, while only two steroids (more polar than cortisol) were found in the adrenal effluent of the normal controls. Evidence is presented for the tentative identification of each steroid. The major compound (32%) in the hypertensive group was 11β, 17α, 20β, 21-tetrahydroxy-pregn-4-en-3-one (20β-OH-cortisol).*** Those compounds that appeared in both groups were about 50% higher in the hypertensive group.
L. E. Hanssen, J. Brownell, J. Halse, J. Jervell, K. T. Stokke, S. Reinlie and S. Stray-Pedersen
Abstract. Current drugs used for hyperprolactinemia may have severe side effects. Effects and side effects of a new propylergoline derivate (CQP 201-403 SANDOZ®) have been evaluated. Twenty-four otherwise healthy women (21–44 years) with hyperprolactinemia (35–318 μg/l) without extrasellar extension of pituitary adenomas took part in a randomized, doubleblind study. Fasting prolactin levels measured on day 7 was significantly decreased when compared with day 1 (P < 0.05) in all CQP groups, to 78% with 0.005 mg daily, to 40% with 0.015 mg daily, and to 27% with 0.025 mg CQP per day for one week. The levels in the control group did not change (96%). The area under the curve of the prolactin day curve (1–8 h after drug administration) decreased significantly (P < 0.05) at all doses when day 7 was compared with day 1, to 77% with 0.005 mg, to 51% with 0.015 mg, and to 37% with 0.025 mg CQP. No change was seen in the control group (96%). Four patients (one on 0.005 mg, one on 0.015 mg, and two on 0.025 mg) experienced orthostatic hypotension while standing blood pressure was to be measured on the first day of treatment, and they had to lie down. CQP 201-403 lowers prolactin levels in hyperprolactinemic women at all doses employed. The effect was seen after the first dose of treatment, and lasted for at least 24 h. The adverse reactions are few and tolerable, and might be less than with current bromocriptine therapy.