Correlation between inhibitory effect on prolactin secretion and antitumor activity of new ergoline compounds on...

Five recently synthesized (355/1057, 355/1000, 355/1101, 355/1138 and FCE 21336) and 4 well-known (bromocriptine, metergoline, 1-demethylmetergoline and pergolide) prolactin-lowering ergoline derivatives and 1 ergoline (nicergoline) without antiprolactin activity were tested against 7-12-dimethyl-benzanthracene (DMBA)-induced mammary carcinomas in rats. Nicergoline did not show any activity, while the other compounds, tested at doses inhibiting prolactin secretion, proved active against established tumors and on the onset of new tumors. The activity of 3 of the new ergolines (355/1000, 355/1057 and FCE 21336) and of bromocriptine and pergolide was also tested at different oral doses and was correlated with serum prolactin levels 24 hr after the last dose. All the compounds proved highly effective, inducing 50-60% regression of the initial tumors. The inhibition of serum prolactin levels was dose-related and, for all the compounds tested except bromocriptine, a good correlation was found between doses administered and complete tumor remissions.