Revision of the Unstable Picrotoxinin Hydrolysis Product

The plant metabolite picrotoxinin (PXN) is a widely used tool in neuroscience for the identification of GABAergic signaling. Its hydrolysis in weakly alkaline media has been observed for over a century and the structure of the unstable hydrolysis intermediate was assigned by analogy to the degradation product picrotoxic acid. Here we show this assignment to be in error and we revise the structure of the hydrolysis product by spectroscopic characterization in situ. Counterintuitively, hydrolysis occurs at a lactone that remains closed in the major isolable degradation product, which accounts for the longstanding mistake in the literature.

Automated summary

The plant metabolite picrotoxinin (PXN) is commonly used in neuroscience to study GABAergic signaling. The hydrolysis of PXN in weakly alkaline media actually occurs at a closed lactone, contributing to a longstanding misunderstanding in the literature.