Chirality and anaesthetic drugs: A review and an update

Abstract

Many molecules can exist as right-handed and left-handed forms that are non-superimposable mirror images of each other. They are known as enantiomers or substances of opposite shape. Such compounds are also said to be chiral (Greek chiros meaning ‘hand’). Such chiral molecules are of great relevance to anaesthetic theory and practice. This review summarizes the basic concepts, pharmacokinetic and pharmacodynamic aspects of chirality, and some specific examples of their application in anaesthesia, along with recent advances to elucidate the anaesthetic mechanisms. Chirality is relevant to anaesthesia, simply because more than half of the synthetic agents used in anaesthesia practice are chiral drugs. Almost all these synthetic chiral drugs are administered as racemic mixture, rather than as single pure enantiomers. These mixtures are not drug formulations containing two or more therapeutic substances, but combination of isomeric substances, with the therapeutic activity residing mainly in one of the enantiomer. The other enantiomer can have undesirable properties, have different therapeutic activities or be pharmacologically inert. Specific examples of application of chirality in anaesthetic drugs include inhalational general anaesthetics (e.g. isoflurane), intravenous anaesthetics (e.g. etomidate, thiopentone), neuromuscular blocking agents (e.g. cisatracurium), local anaesthetics (e.g. ropivacaine and levobupivacaine) and other agents (e.g. levosimendan, dexmedetomidine, L-cysteine). In the recent advances, chirality study has not only helped new drug development as mentioned above, but has also contributed in a more profound way to the understanding of the mechanism of anaesthesia and anaesthetic drugs.

Chirality Status Of Registered Medicines In Tanzania: A Retrospective Cross-Sectional Study

“…Within the classi cation of chiral medicines, racemates (74%) predominated with single enantiomer medicines (26%). These ndings contrast most of studies that indicate an increased number of single enantiomer drugs and only 25-40% of medicines are used as racemic medicines [15,32]. A review on chirality done in Japan [19] and in United Kingdom (UK) [33] reported the tendency of registration approval of medicines has been observed to be towards chiral switching or development of the pure enantiomer.…”

<b>Molecular Discrimination of Barbital Enantiomer at the Propofol Binding Site of the Human β₃ Homomeric GABA_A Receptor </b>

“…In clinical practice, barbital anesthetics are provided as a racemi mixture without specifying the enantiomeric ratio. For further safety in anesthetic development, enantiomeric ratio control is indispensable together with clarifying the action and side actions of individual enantiomers [1].…”

Practical Synthesis of both Enantiomeric Amino Acid, Mannich, and Aldol Derivatives by Asymmetric Organocatalysis

“…The phenomenon of chirality plays an important role in the life of animals and plants in addition to pharmaceutical, agrochemical and other chemical industries . Many compounds associated with living organisms including proteins, enzymes, carbohydrates, nucleosides, alkaloids, and hormones are chiral.…”