Comparative pharmacology of the optical isomers of ketamine in mice.

Relative pharmacological potencies of the optical isomers of ketamine have been estimated in ICR mice. The (+)-isomer was 3X more potent than (-)-ketamine as an analgesic using the phenylquinone writhing test, only 1.5X more potent in terms of hypnotic activity and 1.8X more potent in causing locomotor stimulation. At equianalgesic doses (+)-ketamine caused less stimulation of locomotor activity than the (-)-isomer. These potency differences did not appear to be due to differences in biodisposition although stereoselective metabolism was demonstrated in vivo. Analgesia induced by ketamine was reversed by 10 mg/kg of naloxone.

[1]  L. Gunne,et al.  Stereoselective metabolism of amphetamine. , 1967, Biochemical pharmacology.

[2]  A. Finck,et al.  Nitrous oxide "analgesia": resemblance to opiate action. , 1976, Science.

[3]  F. Wilcoxon,et al.  A simplified method of evaluating dose-effect experiments. , 1948, The Journal of pharmacology and experimental therapeutics.

[4]  R. Cadmus,et al.  A Method for Evaluating both Non-Narcotic and Narcotic Analgesics , 1957, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[5]  A. Finck,et al.  Antagonism of general anesthesia by naloxone in the rat. , 1977, Anesthesiology.

[6]  E F Domino,et al.  Dissociative Anesthesia: Further Pharmacologic Studies and First Clinical Experience with the Phencyclidine Derivative Cl‐581 , 1966, Anesthesia and analgesia.

[7]  A. Glazko,et al.  Biotransformation and Disposition of Ketamine , 1974, International anesthesiology clinics.

[8]  P. White,et al.  Biodisposition of ketamine in the rat: self-induction of metabolism. , 1976, The Journal of pharmacology and experimental therapeutics.

[9]  D. Segal,et al.  Behavioral characterization of d- and l-amphetamine: neurochemical implications , 1975, Science.

[10]  E. Domino,et al.  Pharmacologic effects of CI‐581, a new dissociative anesthetic, in man , 1965, Clinical pharmacology and therapeutics.

[11]  M. Cohen,et al.  Distribution in the Brain and Metabolism of Ketamine in the Rat after Intravenous Administration , 1973, Anesthesiology.

[12]  R. T. Williams,et al.  The metabolic fate of amphetamine in man and other species. , 1970, The Biochemical journal.

[13]  H. Schwertner,et al.  Naloxone-induced inhibition of ethanol dependence in mice , 1977, Nature.

[14]  A. Glazko,et al.  A gas chromatographic assay for ketamine in human plasma. , 1972, Anesthesiology.

[15]  P. Portoghese.  Stereochemical factors and receptor interactions associated with narcotic analgesics. , 1966, Journal of pharmaceutical sciences.

[16]  A. Shulgin.  Stereospecific requirements for hallucinogenesis , 1973, The Journal of pharmacy and pharmacology.

[17]  C. Ensor,et al.  GENERAL ANESTHETIC AND OTHER PHARMACOLOGICAL PROPERTIES OF 2-(O-CHLOROPHENYL)-2-METHYLAMINO CYCLOHEXANONE HCL (CI-58L). , 1965, The Journal of new drugs.

[18]  D. J. Finney.  Statistical Method in Biological Assay , 1966 .

[19]  M. Sadove,et al.  Analgesic Effects of Ketamine Administered in Subdissociative Doses , 1971, Anesthesia and analgesia.

[20]  W. L. Way,et al.  On the pharmacology of the ketamine enantiomorphs in the rat. , 1977, The Journal of pharmacology and experimental therapeutics.