General Anesthetics: Aspects of Chirality, Pharmacodynamics, and Pharmacokinetics

The introduction of general anesthetics in the mid-19th century is considered one of the greatest contributions to medical practice. It was the first time that complicated surgical interventions became feasible, without putting an excessive strain on the patient. The first general anesthetics-diethyl ether, chloroform, and nitrous oxide-were limited by often severe adverse reactions and a narrow therapeutic window. They were later succeeded by modern anesthetics, with high anesthetic effect along with diminished toxicity. As with other medical drugs, many anesthetic compounds contain chiral centers in their molecules. Although currently used as racemates, the pharmacological activity of the respective enantiomerically pure antipodes can vary considerably, as can their adverse effects. Herein, we report on the available studies into the differences in bioactivity and toxicity between the enantiomers of chiral anesthetic agents. Both inhalational and intravenous anesthetics are discussed. Aspects of pharmacodynamics and pharmacokinetics are surveyed as well. The results could stimulate further research into the potential application of single-enantiomer anesthetics in clinical practice.