Effect of Sodium NItroprusside (SNP) on R,S] and S]Ketamine]induced psychotropic side effects, hemodynamic changes and pain relief in healthy volunteers

The aim of this study is to evaluate whether the NO donor SNP prevents the occurrence of psychomimetic side effects without affecting ketamine induced analgesia.

(1) SNP will reduce the occurrence of psychomimetic side effects during exposure to low]dose ketamine;

(2) SNP will reduce the ketamine]induced increase in blood pressure and cardiac output;

(3) SNP is without effect on ketamine]induced pain relief;

(4) SNP is effective in reducing negative effects in both S]ketamine and RS]ketamine treated subjects.

1 hr of SNP adminstration 3 hrs of ketamine adminsitration in three concentrations. Psychomimetic side effects evaluated by questionaire will be evaluated at 15 min. intervals.

Analgesia will be evaluated at 15 min. intervals.
arterial samples will be obtained per protocol at intervals used for pharmacokinetic studies.

Part 1: Sodium nitroprusside(SNP) or placebo will be administered intravenously started 60 minutes prior to intravenous administration of ketamine, and will be terminated when the ketamine infusion is ended. S-ketamine will be administered one hour 10mg/h, one hour 20mg/h, and one hour 40mg/h. R,S-ketamine will be administered one hour 20mg/h, one hour 40mg/h, and one hour 80mg/h.
Part 2: Ketamine (S-or R,S) will be administered intravenously 50mg/h and will be terminated after SNP is given for one hour. Concomitantly placebo infusion will be started, after one hour the placebo infusion will be replaced by SNP for one hour. (Single blinded).