Glycine transporter inhibitor attenuates the psychotomimetic effects of ketamine in healthy males: Preliminary evidence

Neuropsychopharmacology

Volumn 37, Issue 4, 2012, Pages 1036-1046

  D'Souza, Deepak Cyril ^a,b   Singh, Nagendra ^a   Elander, Jacqueline ^a   Carbuto, Michelle ^a,b   Pittman, Brian ^a,b   De Haes, Joanna Udo ^c   Sjogren, Magnus ^c   Peeters, Pierre ^c   Ranganathan, Mohini ^a,b   Schipper, Jacques ^c  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b Yale Medical Group   (United States)

^c NV ORGANON   (Netherlands)

Author keywords

cognition; glycine transporter inhibitor; healthy subjects; ketamine; ORG 25935; psychosis

Indexed keywords

CIS N METHYL N 6 METHOXY 1 PHENYL 1,2,3,4 TETRAHYDRONAPHTHALEN 2 YLMETHYL; GLYCINE TRANSPORTER 1; KETAMINE; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BEHAVIOR CHANGE; CLINICAL ARTICLE; COGNITION; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; HUMAN; MALE; NORMAL HUMAN; PERCEPTION; POSITIVE AND NEGATIVE SYNDROME SCALE; PRIORITY JOURNAL; PSYCHOSIS; RANDOMIZED CONTROLLED TRIAL; SCHIZOPHRENIA;

ADULT; ANESTHETICS, DISSOCIATIVE; CROSS-OVER STUDIES; GLYCINE PLASMA MEMBRANE TRANSPORT PROTEINS; HUMANS; KETAMINE; MALE; PILOT PROJECTS; PSYCHOSES, SUBSTANCE-INDUCED; TETRAHYDRONAPHTHALENES; YOUNG ADULT;

EID: 84857039780     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2011.295     Document Type: Article

References (69)

1. Alberati D, Borroni EDM, Hainzl D, Pinard E, Wettstein JG (2011). Partial Occupancy of the Glycine Transporter Type 1 (GLYT1) Inhibitor in Rat by RG1678 Leads to Efficacy in Models Relevant to Schizophrenia. 13th International Congress on Schizophrenia Research, Colorado Springs, CO.
2. Anand A, Charney DS, Oren DA, Berman RM, Hu XS, Cappiello A et al (2000). Attenuation of the neuropsychiatric effects of ketamine with lamotrigine: Support for hyperglutamatergic effects of N-methyl-Daspartate receptor antagonists. Arch Gen Psychiatry 57: 270-276. (Pubitemid 30140436)
3. Aragon C, Lopez-Corcuera B (2005). Glycine transporters: Crucial roles of pharmacological interest revealed by gene deletion. Trends Pharmacol Sci 26: 283-286. (Pubitemid 40733520)
4. Becker CM, Betz H, Schroder H (1993). Expression of inhibitory glycine receptors in postnatal rat cerebral cortex. Brain Res 606: 220-226. (Pubitemid 23098370)
5. Betz H, Gomeza J, Armsen W, Scholze P, Eulenburg V (2006). Glycine transporters: Essential regulators of synaptic transmission. Biochem Soc Trans 34: 55-58. (Pubitemid 43235533)
6. Borowsky B, Hoffman BJ (1998). Analysis of a gene encoding two glycine transporter variants reveals alternative promoter usage a novel gene structure. J Biol Chem 273: 29077-29085. (Pubitemid 28507604)
7. Borowsky B, Mezey E, Hoffman BJ (1993). Two glycine transporter variants with distinct localization in the CNS peripheral tissues are encoded by a common gene. Neuron 10: 851-863. (Pubitemid 23152041)
8. Bremner JD, Krystal JH, Putnam FW, Southwick SM, Marmar C, Charney DS et al (1998). Measurement of dissociative states with the Clinician-Administered Dissociative States Scale (CADSS). J Trauma Stress 11: 125-136. (Pubitemid 28097797)
9. Brunner E, Domhof S, Langer F (2002). Nonparametric Analysis of Longitudinal Data in Factorial Experiments. 1st edn. John Wiley and Sons: New York, NY.
10. Chattipakorn SC, McMahon LL (2003). Strychnine-sensitive glycine receptors depress hyperexcitability in rat dentate gyrus. J Neurophysiol 89: 1339-1342. (Pubitemid 36323981)
11. Chen L, Muhlhauser M, Yang CR (2003). Glycine tranporter-1 blockade potentiates NMDA-mediated responses in rat prefrontal cortical neurons in vitro and in vivo. J Neurophysiol 89: 691-703. (Pubitemid 36206118)
12. Cho H, Edward Perry E, Gunduz-Bruce H, D'Souza DC (2008). The ketamine paradigm in humans: Relevance to psychotic disorders. In: Heresco-Levy E, Javitt DC (eds). Glutamate in Neuropsychiatric Disorders. Research Signpost: Trivandrum, Kerala, India. pp 99-131.
13. Contreras PC (1990). -serine antagonized phencyclidine-And MK-801-induced stereotyped behavior and ataxia. Neuropharmacology 29: 291-293. (Pubitemid 20096394)
14. D'Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT et al (2004). The psychotomimetic effects of intravenous delta-9-tetrahydrocannabinol in healthy individuals: Implications for psychosis. Neuropsychopharmacology 29: 1558-1572. (Pubitemid 38982249)
15. D'Souza DC, Ranganathan M, Elander J, Carbuto M, Pittman B, Jaeger J et al (2010). Interactive Behavioral Cognitive Effects of Nicotine Ketamine in Healthy Humans Subjects: Implications for Understanding Smoking Schizophrenia. Schizophrenia International Research Society Meeting, Florence.
16. Dingledine R, Kleckner NW, McBain CJ (1990). The glycine coagonist site of the NMDA receptor. Adv Exp Med Biol 268: 17-26.
17. Folstein MF, Folstein SE, McHugh PR (1975). 'Mini-mental state'. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12: 189-198.
18. Gozzi A, Herdon H, Schwarz A, Bertani S, Crestan V, Turrini G et al (2008). Pharmacological stimulation of NMDA receptors via co-Agonist site suppresses fMRI response to phencyclidine in the rat. Psychopharmacology (Berl) 201: 273-284.
19. Harsing Jr. LG, Gacsalyi I, Szabo G, Schmidt E, Sziray N, Sebban C et al (2003). The glycine transporter-1 inhibitors NFPS and Org 24461: A pharmacological study. Pharmacol Biochem Behav 74: 811-825. (Pubitemid 36351646)
20. Hashimoto K, Fujita Y, Ishima T, Chaki S, Iyo M (2008). Phencyclidine-induced cognitive deficits in mice are improved by subsequent subchronic administration of the glycine transporter-1 inhibitor NFPS and D-serine. Eur Neuropsychopharmacol 18: 414-421. (Pubitemid 351608551)
21. Hayashi F, Takahashi K, Nishikawa T (1997). Uptake of D-And L-serine in C6 glioma cells. Neurosci Lett 239: 85-88. (Pubitemid 28060206)
22. Javitt DC, Balla A, Burch S, Suckow R, Xie S, Sershen H (2004). Reversal of phencyclidine-induced dopaminergic dysregulation by N-methyl-D-Aspartate receptor/glycine-site agonists. Neuropsychopharmacology 29: 300-307. (Pubitemid 38175148)
23. Javitt DC, Frusciante M (1997). Glycyldodecylamide, a phencyclidine behavioral antagonist, blocks cortical glycine uptake: Implications for schizophrenia and substance abuse. Psychopharmacology 129: 96-98. (Pubitemid 27037457)
24. Javitt DC, Sershen H, Hashim A, Lajtha A (1997). Reversal of phencyclidine-induced hyperactivity by glycine and the glycine uptake inhibitor glycyldodecylamide. Neuropsychopharmacology 17: 202-204. (Pubitemid 27365961)
25. Kanahara N, Shimizu E, Ohgake S, Fujita Y, Kohno M, Hashimoto T et al (2008). Glycine and D-serine, but not D-cycloserine, attenuate prepulse inhibition deficits induced by NMDA receptor antagonist MK-801. Psychopharmacology (Berl) 198: 363-374.
26. Kantrowitz JT, Javitt DC (2010). N-methyl-D-Aspartate (NMDA) receptor dysfunction or dysregulation: The final common pathway on the road to schizophrenia? Brain Res Bull 83: 108-121.
27. Karasawa J-I, Hashimoto K, Chaki S (2008). d-serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats. Behav Brain Res 186: 78-83. (Pubitemid 350100896)
28. Kay SR, Opler LA, Lindenmayer JP (1989). The Positive and Negative Syndrome Scale (PANSS): Rationale and standardisation. Br J Psychiatry (Suppl) 59-67.
29. Kinney GG, Sur C, Burno M, Mallorga PJ, Williams JB, Figueroa DJ et al (2003). The glycine transporter type 1 inhibitor N-[3-(40-fluorophenyl)-3-(40- phenylphenoxy)propyl]sarcosine potentiates NMDA receptor-mediated responses in vivo and produces an antipsychotic profile in rodent behavior. J Neurosci 23: 7586-7591. (Pubitemid 37034075)
30. Kohr G (2006). NMDA receptor function: Subunit composition versus spatial distribution. Cell Tissue Res 326: 439-446. (Pubitemid 44435819)
31. Konradsson A, Marcus MM, Hertel P, Svensson TH, Jardemark KE (2006). Inhibition of the glycine transporter GlyT-1 potentiates the effect of risperidone, but not clozapine, on glutamatergic transmission in the rat medial prefrontal cortex. Synapse 60: 102-108. (Pubitemid 43878118)
32. Krupitsky EM, Burakov AM, Romanova TN, Grinenko NI, Grinenko AY, Fletcher J et al (2001). Attenuation of ketamine effects by nimodipine pretreatment in recovering ethanol dependent men: Psychopharmacologic implications of the interaction of NMDA and L-type calcium channel antagonists. Neuropsychopharmacology 25: 936-947. (Pubitemid 34031898)
33. Krystal JH, Abi-Saab W, Perry E, D'Souza DC, Liu N, Gueorguieva R et al (2004). Preliminary evidence of attenuation of the disruptive effects of the NMDA glutamate receptor antagonist, ketamine, on working memory by pretreatment with the group II metabotropic glutamate receptor agonist, LY354740, in healthy human subjects. Psychopharmacology (Berl) 179: 303-309. (Pubitemid 40576718)
34. Krystal JH, D'Souza DC, Karper LP, Bennett A, Abi-Dargham A, Abi-Saab D et al (1999). Interactive effects of subanesthetic ketamine and haloperidol in healthy humans. Psychopharmacology (Berl) 145: 193-204. (Pubitemid 29362018)
35. Krystal JH, Karper LP, Bennett A, D'Souza DC, Abi-Dargham A, Morrissey K et al (1998a). Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans. Psychopharmacology (Berl) 135: 213-229. (Pubitemid 28055456)
36. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD 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. (Pubitemid 24081509)
37. Krystal JH, Perry E, Gueorguieva R, Belger A, Madonick S, Abi-Dargham A et al (2005a). Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: Implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch Gen Psychiatry 62: 985-994.
38. Krystal JH, Perry Jr. EB, Gueorguieva R, Belger A, Madonick SH, Abi-Dargham A et al (2005b). Comparative and interactive human psychopharmacologic effects of ketamine and amphetamine: Implications for glutamatergic and dopaminergic model psychoses and cognitive function. Arch Gen Psychiatry 62: 985-994.
39. Krystal JH, Petrakis IL, Webb E, Cooney NL, Karper LP, Namanworth S et al (1998b). Dose-related ethanol-like effects of the NMDA antagonist, ketamine, in recently detoxified alcoholics. Arch Gen Psychiatry 55: 354-360. (Pubitemid 28173625)
40. Lahti AC, Koffel B, LaPorte D, Tamminga CA (1995). Subanesthetic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology 13: 9-19.
41. Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA (2001). Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 25: 455-467. (Pubitemid 32830950)
42. Leung S, Croft RJ, O'Neill BV, Nathan PJ (2008). Acute high-dose glycine attenuates mismatch negativity (MMN) in healthy human controls. Psychopharmacology (Berl) 196: 451-460. (Pubitemid 351191176)
43. Liu L, Wong TP, Pozza MF, Lingenhoehl K, Wang Y, Sheng M et al (2004). Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science 304: 1021-1024. (Pubitemid 38638102)
44. Loftis JM, Janowsky A (2003). The N-methyl-D-Aspartate receptor subunit NR2B: Localization, functional properties, regulation, and clinical implications. Pharmacol Ther 97: 55-85. (Pubitemid 35477804)
45. Lynch DR, Guttmann RP (2002). Excitotoxicity: Perspectives based on N-methyl-D-Aspartate receptor subtypes. J Pharmacol Exp Ther 300: 717-723. (Pubitemid 34164971)
46. MacDonald JF, Jackson MF, Beazely MA (2006). Hippocampal long-term synaptic plasticity and signal amplification of NMDA receptors. Crit Rev Neurobiol 18: 71-84. (Pubitemid 350194079)
47. Malhotra AK, Pinals DA, Adler CM, Elman I, Clifton A, Pickar D et al (1997). Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology 17: 141-150. (Pubitemid 27365955)
48. Malhotra AK, Pinals DA, Weingartner H, Sirocco K, Missar CD, Pickar D et al (1996). NMDA receptor function and human cognition: The effects of ketamine in healthy volunteers. Neuropsychopharmacology 14: 301-307. (Pubitemid 26151927)
49. Malosio ML, Marqueze-Pouey B, Kuhse J, Betz H (1991). Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO J 10: 2401-2409. (Pubitemid 21905713)
50. Mohler H, Rudolph U, Boison D, Singer P, Feldon J, Yee BK (2008). Regulation of cognition and symptoms of psychosis: Focus on GABA(A) receptors and glycine transporter 1. Pharmacol Biochem Behav 90: 58-64.
51. Morgan CJ, Perry EB, Cho HS, Krystal JH, D'Souza DC (2006). Greater vulnerability to the amnestic effects of ketamine in males. Psychopharmacology (Berl) 187: 405-414. (Pubitemid 44200512)
52. Nilsson M, Carlsson A, Carlsson ML (1997). Glycine and D-serine decrease MK-801-induced hyperactivity in mice. J Neural Transm 104: 1195-1205. (Pubitemid 28031813)
53. O'Neill BV, Croft RJ, Mann C, Dang O, Leung S, Galloway MP et al (2010). High-dose glycine impairs the prepulse inhibition measure of sensorimotor gating in humans. J Psychopharmacol; e-pub ahead of print 8 July 2010.
54. Priestley T, Kemp JA (1994). Kinetic study of the interactions between the glutamate and glycine recognition sites on the N-methyl-Daspartic acid receptor complex. Mol Pharmacol 46: 1191-1196.
55. Racca C, Gardiol A, Triller A (1998). Cell-specific dendritic localization of glycine receptor alpha subunit messenger RNAs. Neuroscience 84: 997-1012. (Pubitemid 28157019)
56. Rey A (1958). L'Examen Clinique en Psychologie. Press Universitaire de France: Paris.
57. Ribeiro CS, Reis M, Panizzutti R, de Miranda J, Wolosker H (2002). Glial transport of the neuromodulator D-serine. Brain Res 929: 202-209. (Pubitemid 34178335)
58. Roberts BM, Shaffer CL, Seymour PA, Schmidt CJ, Williams GV, Castner SA (2010). Glycine transporter inhibition reverses ketamineinduced working memory deficits. Neuroreport 21: 390-394.
59. Sahakian BJ, Owen AM (1992). Computerized assessment in neuropsychiatry using CANTAB: Discussion paper. J R Soc Med 85: 399-402.
60. Snigdha S, Shahid M, Grayson B, Marston HM, Neill JC (2007). A potential role for glycine transport inhibitors in ameliorating cognitive dysfunction in schizophrenia: Effects of Org 25935. Schizophr Bull 33: 542.
61. Tanii Y, Nishikawa T, Hashimoto A, Takahashi K (1991). Stereoselective inhibition by D-And L-Alanine of phencyclidineinduced locomotor stimulation in the rat. Brain Res 563: 281-284.
62. Tanii Y, Nishikawa T, Hashimoto A, Takahashi K (1994). Stereoselective antagonism by enantiomers of alanine and serine of phencyclidine-induced hyperactivity, stereotypy and ataxia in the rat. J Pharmacol Exp Ther 269: 1040-1048. (Pubitemid 24204184)
63. Thio LL, Shanmugam A, Isenberg K, Yamada K (2003). Benzodiazepines block alpha2-containing inhibitory glycine receptors in embryonic mouse hippocampal neurons. J Neurophysiol 90: 89-99. (Pubitemid 36859161)
64. Thomson AM (1990). Glycine is a coagonist at the NMDA receptor/channel complex. Prog Neurobiol 35: 53-74. (Pubitemid 20228554)
65. Toth E, Lajtha A (1986). Antagonism of phencyclidine-induced hyperactivity by glycine in mice. Neurochem Res 11: 393-400. (Pubitemid 16129125)
66. Umbricht D (2010). Glycine Transporter Type 1 (GLYT1) Inhibitor RG1678: Positive Results of the Proof-of-Concept Study for the Treatment of Negative Symptoms in Schizophrenia'. 49th Annual Meeting of the American College of Neuropsychopharmacology, Miami Beach, FL.
67. Walker GB, Ge J, Cruise L, Hamilton W, Bruin J, Henry B et al (2007). Characterization of Org 25935: A selective GlyT-1 glycine uptake inhibitor. Schizophr Bull 33: 325.
68. Zhang LH, Gong N, Fei D, Xu L, Xu TL (2008a). Glycine uptake regulates hippocampal network activity via glycine receptormediated tonic inhibition. Neuropsychopharmacology 33: 701-711.
69. Zhang Z, Gong N, Wang W, Xu L, Xu TL (2008b). Bell-shaped D-serine actions on hippocampal long-term depression and spatial memory retrieval. Cereb Cortex 18: 2391-2401.