Novel 8 alpha-ergolines with inhibitory and stimulatory effects on prolactin secretion in rats.

Abstract

Four derivatives of the ergot dopamine (DA) agonist lisuride (LIS), namely 6-n-propyl-lisuride (6-n-propyl-LIS), transdihydrolisuride (TDHL), 6-n-propyl-transdi-hydrolisuride (6-n-propyl-TDHL) and 2-bromolisuride (2-Br-LIS) were investigated in female rats with regard to their influence on hyperprolactinaemia induced by pretreatment with reserpine (2 mg/kg i.p., 24 h) at various intervals following their subcutaneous or oral administration (0.05 mg/kg). Two hours after administration, LIS, 6-n-propyl-LIS, and 6-n-propyl-TDHL caused a statistically significant inhibition of reserpine-induced hyperprolactinaemia of about the same extent. Eight hours after administration 6-n-propyl-LIS and 6-n-propyl-TDHL were as active as after 2 h in inhibiting prolactin (PRL) secretion whereas LIS was almost ineffective in this respect. TDHL caused a statistically significant inhibition of PRL secretion at 2 and 8 h after oral administration; this effect was less pronounced after s.c. administration. In contrast to the aforementioned derivatives 2-Br-LIS further increased the reserpine-induced hyperprolactinaemia. In normal male rats pretreatment with 2-Br-LIS (0.025-6.25 mg/kg s.c., 2 h) dose-dependently stimulated PRL secretion. The present data support the assumption of the longlasting DA agonistic action of 6-n-propyl-LIS and 6-n-propyl-TDHL and of the antidopaminergic properties of 2-Br-LIS recently derived from behavioural studies.

• Authors: H Wachtel, R Dorow, G Sauer
• Journal: Life sciences (Life Sci) Vol. 35 Issue 18 Pg. 1859-67 (Oct 29 1984) ISSN: 0024-3205 [Print] Netherlands
• PMID: 6492995 (Publication Type: Journal Article)

Chemical References

• Ergolines
• Prolactin
• Lisuride

Topics

• Animals
• Ergolines (pharmacology)
• Female
• Lisuride (analogs & derivatives, pharmacology)
• Male
• Prolactin (blood, metabolism)
• Rats
• Rats, Inbred Strains
• Structure-Activity Relationship