Progress in the development of ultra-long-acting local anesthetics.
Local anesthetic agents with a duration of action longer than the currently available local anesthetics could have widespread clinical application for the treatment of both chronic and acute pain. Over the last several decades, several different approaches have been used in the development of ultra-long-acting agents. There are currently promising preparations in development which may prove clinically useful in the near future. A Medline search was conducted for relevant articles published in peer-reviewed journals between 1971 and 1996. Investigations related to prolongation of the effect of local anesthetics either by alterations in the local anesthetic molecule, use of new or novel agents, or use of new delivery systems were reviewed. In addition, bibliographies of relevant articles were searched to capture any articles that were missed by the Medline search. Over the last several decades, numerous attempts have been made to prolong the duration of action of local anesthetics. Initially, research focused on alterations in the local anesthetic molecule or the identification of new agents with local anesthetic action. Recently, the focus of much of the work has shifted to new drug-delivery systems such as polymers and liposomes. Although encouraging results have been reported in the literature, there is currently no agent or delivery system that has shown reliable and practical prolongation of local anesthetic effect in humans. There have been several encouraging reports in animals that have shown local anesthetic effects lasting up to several days, but these results must be validated and then performed in human studies before a clinically useful agent is found. Further research is warranted.