Tetraethylammonium derivatives: ultralong-acting local anesthetics?

Derivatives of tetraethylammonium ion (TEA+) were synthesized in which one ethyl group was replaced by a C6, C8, C10, C12, C14, or C16 side chain. These TEA+ derivatives were tested for duration of sensory block of the rat infraorbital (trigeminal) nerve. The duration of sensory anesthesia increased exponentially from 1.2 hours to 388 hours as chain length increased from C2-C12, while C12, C14, and C16 all produced a similar reversible block of 17--20 days. The block duration of C12 was correlated with C12 bound to the infraorbital nerve; C12 not bound by the nerve was quantitatively excreted by the kidneys. These data, along with the lack of observable microscopic toxicity, suggests that TEA+ derivatives may be a useful new class of ultralong-acting local anesthetics.