Nuclear Magnetic Resonance Evidence for Interactions between Procaine and Thiamine Pyrophosphate

Abstract

ECKERT^1,2 reported that procaine and other local anaesthetics form pi-electron complexes with thiamine, and he suggested that such complexes in nerves might be responsible for local anaesthesia. Eckert's evidence for the procaine–thiamine interaction was based on the appearance of “charge transfer” bands in the ultraviolet absorption spectra of thiamine–procaine mixtures. Agin³, however, repeated Eckert's experiments and reported that the “charge transfer” bands were artefacts produced by the spectrophotometric analysis. Recent findings by Itokawa and Cooper⁴ are compatible with the long held hypothesis⁵ that thiamine and its phosphate esters have specific functions in conduction processes of nerve tissue that are independent of the known coenzyme roles of these compounds. Interaction between local anaesthetics and thiamine thus remains a likely chemical mechanism for local anaesthesia. Thiamine present in nervous tissue is largely in the form of thiamine pyrophosphate (TPP)⁴. We have investigated the possibility of binding between TPP and procaine by means of a nuclear magnetic resonance (NMR) technique found valuable in studying interactions between small molecules containing aromatic groups⁶.