Biological properties of 2-phenyl-3-p-(β-pyrrolidinoethoxy)-phenyl-(2:1,b) naphthofuran — A new oral antifertility agent

Abstract

The biologic properties of a new oral antifertility agent, 2-phenyl-3-p-(β-pyrrolidinoethoxy)-phenyl (2:1,b) naphthofuran have been investigated in detail in rodent species and rhesus monkeys ($\text{Macaca mulatta}$). The compound causes 100% prevention of conception in rats, mice, and rhesus monkeys at a single oral dose of 10 mg/kg administered immediately postcoitum; the minimum effective dose (rats) in day 1–5 regime is 2 mg/kg. The antifertility effect is reversible. It shows mild estrogenic (uterotrophic) activity of short duration and slight antiestrogenicity; progestational, androgenic and antiandrogenic properties are absent, but the compound antagonizes progesterone action in ‘delayed implantation’ and ‘deciduoma induction’ tests. The pituitary, thyroid and andrenocortical function, and the menstrual cycle are not disturbed. The compound causes slight foetal resorption but no genital abnormalities or teratogenicity; the post-natal sexual development and subsequent fertility remain unimpaired. It prevents implantation through inhibition of deciduoma formation by virtue of its antiprogestational activity; tubal transport, fertilization, development and viability of ova are unaffected. The compound has a favorable therapeutic index.