Schild analysis of the interaction between parthenolide and cocaine on their effects on planarian motility suggests an orthosteric relationship

Abstract

One of the best-characterized planarian behaviors induced by various compounds is the change in locomotor velocity. Previous work from our laboratory showed that the sesquiterpene lactone parthenolide and the local anesthetic cocaine, reduce planarian motility. Parthenolide reverses the cocaine-induced motility decrease and vice versa. However, the exact mechanism of the cocaine/parthenolide antagonism for this specific planarian behavior is still unknown. Here we report the results of a Schild analysis to determine whether the parthenolide/cocaine relationship is orthosteric or allosteric. Our results suggest an orthosteric relationship between these two compounds in the planarian Girardia tigrina. The simplest interpretation of our data is a shared binding site for cocaine and parthenolide. Still, we cannot rule out the possibility of distinct yet overlapping binding sites with the data available.