R-Ketamine

Davis, S. R. Ketamine in chronic pain a review, Aust. J. Hosp. Pharm. 1999, 28, 94-98. 

SYNS CI 581 CL369 CN-52,372-2 KETAJECT KETAL. R KETAMINE KETAMINE HYDROCHLORIDE KETANEST KETASET KETAVET KETOLAR VETALAR... 

Ketamine is a low-molecular-weight, highly lipid- and water-soluble molecule. As such, it can quickly cross the blood-brain barrier, producing a maximal effect in the CNS within 1 min of i.v. administration. Ketamine exists as a racemic mixture of the two optical isomers S(+)-ketamine and R(-)-ketamine. The majority of the hypnosis and analgesia produced by ketamine is contributed by the S(+)-isomer (Joo et al 2000, Muir Hubbell 1988, Redig et al 1984). A purified S(+)-ketamine pharmaceutical product is not yet available commercially for veterinary use and the possible advantages of such a product in the horse have not been established. Ketamine is 45-60% bound to equine plasma proteins (Kaka et al 1979) meaning that the maximal effect of ketamine is unlikely to be altered substantially by hypoproteinemic states. 

Hirshman CA, Krieger W, Littlejohn G, Lee R, Julien R. Ketamine-aminophylline-induced decrease in seizure threshold. Anesthesiology (1982) 56, 464-7. 

Hoskins R. Ketamine associated cystitis—a case report. Int Emerg Nurs 2009 17(1) 69-71. 

Brecelj J, Trop TK, Orel R. Ketamine with and without midazolam for gastrointestinal endoscopies in children. J Pediatr Gastroenterol Nutr... 

Anis, N.A. Berry, S.C. Burton, N.R. and Lodge, D. The dissociative anaesthetics, ketamine and phencyclidine selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Bj J. Pharmacol 79 565-575, 1983. 

Lodge, D. Anis, N.A. and Burton, N.R. Effects of optical isomers of ketamine on excitation of cat and rat spinal neurons by amino acids and acetylcholine. Neurosci Lett 29 282-286, 1982. 

Chait, L.D. Wenger, G.R. and McMillan, D.E. Effects of phencyclidine and ketamine on punished and unpunished responding in pigeons. Pharmacol Biochem Behav 15 145-148, 1981. 

Hammer, R. P. Herkenham, M. (1983). Altered metabohc activity in the cerebral cortex of rats exposed to ketamine. J. Comp. Neurol. 220, 396-404. 

Hammer, R. P., Jr., Herkenham, M., Pert, C. B., and Quirion, R. (1982) Correlation of regional brain metabolism with receptor localization during ketamine anesthesia Combined autoradiographic 2-(3H)deoxy-D-glucose receptor binding technique. Proc. Natl. Acad. Sci. USA, 79 3067-3070. 

Metabotropic G-protein linked receptors are also modulated by general anesthetics. In particular, the current produced through activation of muscarinic receptors (Ml) for acetylcholine and the serotonergic receptor 5HT2 is inhibited by halothane, isoflurane and enflurane (Lin et al., 1993 Minami et al., 1994 Durieux, 1995). Ketamine inhibits muscarinic receptors although there is no stereospecificity of inhibition (Durieux Nietgen, 1997). The S-isomer of ketamine is more potent as an anesthetic than the R-isomer (Benthuysen et al., 1989). It is thus unlikely that the Ml muscarinic receptor plays a role in... 

Snznki R, Matthews EA, Dickenson AH (2001) Comparison of the effects of MK-801, ketamine and memantine on responses of spinal dorsal horn nenrones in a rat model of mononenropathy. Pain 91 101-109... 

The more active enantiomer at one type of receptor site may not be more active at another receptor type, eg, a type that may be responsible for some other effect. For example, carvedilol, a drug that interacts with adrenoceptors, has a single chiral center and thus two enantiomers (Figure 1-2, Table 1-1). One of these enantiomers, the (S) -) isomer, is a potent B-receptor blocker. The (R)(+) isomer is 100-fold weaker at the receptor. However, the isomers are approximately equipotent as -receptor blockers. Ketamine is an intravenous anesthetic. The (+) enantiomer is a more potent anesthetic and is less toxic than the (-) enantiomer. Unfortunately, the drug is still used as the racemic mixture. 

A putative back-up of this structural class might be AR-R-15,896 which is at least in preclinical development by AstraZeneca (company communication). Compared to ketamine and memantine, AR-R-15,896 might have more favorable pharmacodynamic features (Mealing et al.,... 

Mao, J., Price, D. D., Hayes, R. L., Lu, J., Mayer, D. J., Frenk, H.. Intrathecal treatment with dextmphan or ketamine potently reduces pain-related behaviors in a rat model of peripheral mononeuropathy, Brain Res. 1993, 605, 164-168. 

Vitamin D see Dextromethorphan Vitamin K see Ketamine Vitamin R see Methylphenidate Vivactil see Antidepressants Vivol see Benzodiazepine Volatile solvents see Inhalants... 

H. Y. Aboul-Enein and M. R. Islam, Enantiomeric separation of ketamine hydrochloride in pharmaceutical formulations and human serum by chiral liquid chromatography, J. Liquid Chromatogr., 75 3285(1992). 

Narendran R, Frankie WG, Keefe R, Gil R, Martinez D, et al. 2005. Altered prefrontal dopaminergic function in chronic recreational ketamine users. Am J Psychiatry 162 ... 

Boeijinga PH, Soufflet L, Santoro F, Luthringer R. 2007. Ketamine effects on CNS responses assessed with MEG/ EEG in a passive auditory sensory-gating paradigm An attempt for modelling some symptoms of psychosis in man. J Psychopharmacol 21 321-337. 

Duncan EJ, Madonick SH, Parwani A, Angrist B, Rajan R, et al. 2001. Clinical and sensorimotor gating effects of ketamine in normals. Neuropsychopharmacology 25 72-83. 

Hartvig P, Valtysson J, Lindner KJ, Kristensen J, Karlsten R, Gustafsson LL, Persson J, Svensson JO, Oye I, Antoni G, et al. 1995. Central nervous system effects of subdisso-ciative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission... 

Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, et al. 1994. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 51 199-214. 

Krystal JH, Perry EB Jr., Gueorguieva R, Belger A, Madonick SH, et al. 2005b. Comparative and interactive human psy-chopharmacologic effects of ketamine and amphetamine Implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch Gen Psychiatry 62 985-994. 

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