Pharmacological comparison of R(+), S(-) and racemic thiopentone in mice

The i.p. LD50's of the enantiomorphs of thiopentone have the following increasing order of lethality R(+), racemate and S(-). Whereas the racemate and the S(-) compound have similar therapeutic indices, the R(+) compound has the highest value. The S(-) isomer is the most potent anesthetic agent, followed by the R(+) and the racemate. In the ability to block pentylenetetrazol- and strychnine-induced seizures, the compounds are ranked in the following order of decreased potency: S(-), racemate and R(+). The differences in potency between antipodes have been related to absolute steric configuration of the molecules. Differences in potency of the stereoisomers have been discussed in relationship to known metabolic conversions of thiopentone and its rapid penetration into body fat depots.