1995 Gaston Labat Lecture. Ropivacaine. White knight or dark horse?

Ropivacaine, a new local anesthetic now under Federal Drug Administration review for clinical release, is a unique drug designed to take advantage of cardiac sodium channel stereoselectivity. The Labat lecture, honoring the father of regional anesthesia, pays tribute to the master by tracing the evolution of knowledge transfer from basic science frontiers to safer clinical practice.

A survey was made of pertinent English-language literature on stereoselectivity of bupivacaine isomers and the evaluation and validation of ropivacaine, including a stereoisomerism primer for the nonscientist.

A synopsis of current basic and (pre)clinical findings, preparing North American clinicians for the imminent introduction of ropivacaine, is presented, along with predictions for potential clinical application.

Bupivacaine cardiotoxicity results from prolonged sodium channel dwell time of the R(ectus), as compared with the S(inister), stereoisomer. Bupivacaine, like most aminoamide local anesthetics (except lidocaine), has a chiral (asymmetric) carbon atom where the amide linkage joins the hydrophilic tail. Chirality yields two steric forms (S and R) which are spatial mirror images (like the left hand trapped in a right glove) with different receptor kinetics; commercial bupivacaine is the optically inactive racemic (RS) mixture of R- and S-bupivacaine. Ropivacaine is unique in that membrane separation synthesis exclusively yields the S-monomer, which is a local anesthetic with lower cardiotoxic potential than racemic bupivacaine. Its immediate clinical application would be in obstetric analgesia, whereas its shorter duration of action and weaker motor block should make it useful in ambulatory anesthesia.