Physical and Pharmacological Properties of an Irreversible Local Anesthetic

Gerald M. Rosen, Seymour Ehrenpreis, Thomas W. Mittag, James F. Stubbins

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9 Scopus citations


A systematic investigation of a new class of ultralong-acting local anesthetic was undertaken to determine the active pharmacophore. The thermodynamic constants for the solvolvsis of the aziridinium ion (Ea, ΔH, ΔS) compared favorably with those reported in the literature for other aziridinium type compounds. 2-[(2-Chloro-ethyl)methylamino]ethyl 4-ethoxybenzoate-HCl upon neutralization in a physiological buffered solution blocked irreversibly the indirectly elicited twitch of the rat phrenic nerve-diaphragm preparation without altering either nerve or muscle excitability, suggesting a selective action at the neuromuscular junction at 0.2% and at an exposure time of 30 min. At 0.5%, this compound upon neutralization blocked axonal conduction of the sciatic neree of the frog irreversibly whereas comparable blockade by procaine (1%,) or lidocaine (2%) of this preparation was fully reversible upon washing. It is proposed that the aziridinium ion forms an irreversible bond with a tissue “acceptor” and the stability of this ion determines the effectiveness of drug action.

Original languageEnglish
Pages (from-to)514-516
Number of pages3
JournalJournal of Medicinal Chemistry
Issue number6
StatePublished - 1 Jun 1971
Externally publishedYes


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