Nonpeptide oxytocin agonists

Oxytocin is a neurohypophyseal hormone that acts at the oxytocin receptor localized both peripherally and centrally and is particularly highly expressed in the pregnant human myometrium. Synthetic oxytocin has long been used to induce labor and oxytocin antagonists have been introduced for the treatment of preterm labor. New compounds are described that are potent, selective and efficacious oxytocin receptor agonists with potential utility in promoting labor and for the treatment of conditions such as male and female sexual dysfunction. These new agents may also be useful as tools for further elucidating the roles of the oxytocin receptor system. Furthermore, as they are nonpeptidic in nature, they may offer advantages over peptide oxytocin analogues in terms of oral availability and central penetration. This article describes the various approaches that have been used to discover such compounds. Compounds such as 27, the first nonpeptide oxytocin agonists reported, are currently being investigated as pharmacological tools in animal models of oxytocin activity.