The clinical application of S-(+)-ketamine.

The intravenous anaesthetic ketamine is a racemic mixture of two equimolar doses of enantiomers. After stereoselective separation, the right-handed S(+)-isomer is now clinically available. Since anaesthetic and analgesic pharmacological studies have shown that S(+)-ketamine is approximately two times as potent as racemic ketamine, the clinical effects of S(+)-ketamine were evaluated in comparison to ketamine-racemate at dose relation of 1:2 in several therapeutic investigations. The studies disclosed that both drugs caused a similar activation of the endocrine stress response and a comparable stimulation of the sympathoadrenergic system. However, application of S(+)-ketamine was associated with a remarkably smoother emergence period, a profound postoperative analgesia, a more rapid recovery of cerebral functions, and a greater preference by the study persons. The incidence of psychotomimetic phenomena appeared to be negligibly less after S(+)-ketamine in comparison to racemic ketamine, but their quality was described as far less unpleasant. Clinical use of S(+)-ketamine administered at one-half of the usual dose is thus not only associated with a reduction of undesirable adverse effects without altering ketamine's anaesthetic and analgesic potency, but also offers distinctive improvements due to the reduced drug load. Moreover, increasing experimental evidence supports a remarkable neuroprotective effect of S(+)-ketamine, which may become a promising drug for new therapeutic approaches to neuroprotection.