The distribution and clearance of (2S,6S)-hydroxynorketamine, an active ketamine metabolite, in Wistar rats

Pharmacology Research and Perspectives

Volumn 3, Issue 4, 2015, Pages

  Moaddel, Ruin ^a   Sanghvi, Mitesh ^a   Dossou, Katina Sourou Sylvestre ^a   Ramamoorthy, Anuradha ^a   Green, Carol ^b   Bupp, James ^b   Swezey, Robert ^b   O'Loughlin, Kathleen ^b   Wainer, Irving W ^a  

^a NATIONAL INSTITUTE ON AGING   (United States)

^b SRI INTERNATIONAL   (United States)

Author keywords

Antidepressant; bioavailability of (2S,6S) HNK; brain concentrations; plasma half life and distribution of (2S,6S) HNK

Indexed keywords

HYDROXYNORKETAMINE; KETAMINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BRAIN METABOLISM; CENTRIFUGATION; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; MALE; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PRIORITY JOURNAL; RAT; VALIDATION PROCESS;

EID: 84971240139     PISSN: None     EISSN: 20521707     Source Type: Journal    
DOI: 10.1002/prp2.157     Document Type: Article

References (20)

1. Bolze S, Boulieu R (1998). HPLC determination of ketamine, norketamine and dehydronorketamine in plasma with a high-purity reversed-phase sorbent. Clin Chem 44: 560–564.
2. Cohen ML, Chan S-L, Way WL, Trevor AJ (1973). Distribution in the brain and metabolism of ketamine in the rat after intravenous administration. Anesthesiology 39: 370–376.
3. Desta Z, Moaddel R, Ogburn ET, Xu C, Ramamoorthy A, Venkata SLV, et al. (2012). Stereoselective and regiospecific hydroxylation of ketamine and norketamine. Xenobiotica 42: 1076–1087.
4. Dwyer JM, Duman RS (2013). Activation of mammalian target of rapamycin and synaptogenesis: role in the actions of rapid-acting antidepressants. Biol Psychiatry 73: 1189–1198.
5. Hirota K, Lambert DG (2011). Ketamine: new uses for an old drug? Br J Anaesth 107: 123–126.
6. Leung LY, Baillie TA (1986). Comparative pharmacology in the rat of ketamine and its two principal metabolites, norketamine and (Z)-6-hydroxynorketamine. J Med Chem 29: 2396–2399.
7. Li N, Lee B, Lui R-J, Banasr M, Dwyer JM, Iwata X-Y, et al. (2010). mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329: 959–964.
8. Moaddel R, Venkata SLV, Tanga MJ, Bupp JE, Green CE, LaIyer L, et al. (2010). A parallel chiral-achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome. Talanta 82: 1892–1904.
9. Moaddel R, Abdrakhmanova G, Kozak J, Jozwiak K, Toll L, Jimenez L, et al. (2013). Sub-anesthetic concentrations of (R, S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors. Eur J Pharmacol 698: 228–234.
10. Paul R, Schaaff N, Padberg F, Möller HJ, Frodl T (2009). Comparison of racemic ketamine and S-ketamine in treatment-resistant major depression: report of two cases. World J Biol Psychiatry 10: 241–244. doi:10.1080/15622970701714370
11. Paul RK, Singh NS, Khadeer M, Moaddel R, Sanghvi M, Green CE, et al. 2014. (R,S)-Ketamine metabolites (R,S)-norketamine and (2S,6S)-hydroxynorketamine increase the mammalian target of rapamycin (mTOR) function. Anesthesiology 121:149–159.
12. Rosenberg D, Artoul S, Segal AC, Kolodney G, Radzishevsky I, Dikopoltsev E, et al. (2013). Neuronal D-serine and glycine release via the Asc-1 transporter regulates NMDA receptor-dependent synaptic activity. J Neurosci 33: 3533–3544.
13. Singh NS, Paul RK, Ramamoorthy A, Torjman MC, Moaddel R, Bernier M, et al. (2013a). Nicotinic acetylcholine receptor antagonists alter the function and expression of serine racemase in PC-12 and 1321N1 cells. Cell Signal 25: 2634–2645.
14. Trullas R, Skolnick P. 1990. Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol 185:1–10.
15. Turfus SC, Parkin MC, Cowan DA, Halket JM, Smith NW, Braithwaite RA, Elliot SP, Steventon GB, Kicman AT (2009). Use of human microsomes and deuterated substrates; an alternative approach for the identification of novel metabolites of ketamine by mass spectrometry. Drug Metab Dispos 37: 1769–1778.
16. Williams ML, Mager DE, Parentau H, Gudi G, Tracy TS, Mulhern M, et al. (2004). Effects of protein calorie malnutrition on the pharmacokinetics of ketamine in rats. Drug Metab Dispos 32: 786–793.
17. Zarate CA Jr, Mathews DC, Furey ML (2013). Human biomarkers of rapid antidepressant effects (Review). Biol. Psych. 73: 1142–1155.
18. Zarate CA, Jr, Brutsche N, Laje G, Luckenbaugh DA, Ramamoorthy A, Moaddel R, et al. (2012). Relationship of ketamine's plasma metabolites with response and diagnosis, and side effects in major depression. Biol Psychiatry 72: 331–338.
19. Zhang J-C, Li S-X, Hashimoto K (2014). R (−)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine. Pharmacol Biochem Behavior 116: 137–141.
20. Zhao X, Venkats SLV, Moaddel R, Luckenbaugh DA, Brutsche NE, Ibrahim L, et al. (2012). Simultaneous population pharmacokinetic modeling of ketamine and three major metabolites in patients with treatment-resistant bipolar depression. Br J Clin Pharmacol 74: 304–314.