General anesthetics enantiomers

Although most anesthetics are achiral or are adininistered as racemic mixture, the anesthetic actions are stereoselective. This property can define a specific, rather than a nonspecific, site of action. Stereoselectivity is observed for such barbiturates as thiopental, pentobarbital, and secobarbital. The (3)-enantiomer is modestly more potent (56,57). Additionally, the volatile anesthetic isoflurane also shows stereoselectivity. The (3)-enantiomer is the more active (58). Further evidence that proteins might serve as appropriate targets for general anesthetics come from observations that anesthetics inhibit the activity of the enzyme luciferase. The potencies parallel the anesthetic activities closely (59,60). 

UNDESIRED EEEECTS OF LOCAL ANESTHETICS In addition to blocking conduction in nerve axons in the peripheral nervous system, local anesthetics interfere with the function of all organs in which conduction or transmission of impulses occurs. Thus, they have important effects on the CNS, autonomic ganglia, neuromuscular junctions, and all forms of muscle. The danger of such adverse reactions is proportional to the concentration of local anesthetic achieved in the circulation. In general, in local anesthetics with chiral centers, the -enantiomer is less toxic than the R-enantiomer. 

Figure 1 VCD of desflurane. The experimental spectrum shows the (-)-enantiomer (corrected, as the original label incorrectly read (+) due to a confusion) 0.2 M solution in CCI3). The theoretical calculations were done on the (R) configuration. Reprinted with permission from Polavarapu PL, Cholli AL and Ver-nice G (1992) Determination of absolute configurations and predominant conformations of general inhalation anesthetics desflurane. Journal of Pharmaceutical Sciences 82 791-793. 1992 American Chemical Society.

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