Advanced search
Publication Cover
Expert Opinion on Investigational Drugs Volume 13, 2004 - Issue 5
Submit an article Journal homepage
146
Views
39
CrossRef citations to date
0
Altmetric
Review

The therapeutic potential of glycine transporter-1 inhibitors

Cyrille Sur Merck Research Laboratories, P.O. Box 4, WP44E-200, West Point, PA 194286, USA. [email protected]
&
Gene G Kinney Merck Research Laboratories, P.O. Box 4, WP44E-200, West Point, PA 194286, USA. [email protected]
Pages 515-521 | Published online: 02 Mar 2005

Bibliography

  • APRISON MH: The discovery of the neurotransmitter role of glycine. In: Glycine Neurotransmission. OP Ottersen, J Storm-Mathisen (Eds), John Wiley and Sons, Chichester, UK (1990):1–23.
  • JOHNSON JW, ASCHER P: Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature (1987) 325 (6104):529–531.
  • BETZ H: Ligand-gated ion channels in the brain: the amino acid receptor superfamily. Neuron (1990) 5(4):383–392.
  • BERGERON R, MEYER TM, COYLE JT, GREENE RW: Modulation of N-methyl-D-aspartate receptor function by glycine transport. Proc. Natl. Acad. Sci. USA (1998) (26): 15730–15734. First study to use NFPS to inhibit GlyTl. Demonstrated that G1yT1 inhibition could potentiate NMDA receptor-mediated responses in rat hippocarnpus in vitro.
  • DANYSZ W, PARSONS AC: Glycine and N-methyl-D-aspartate receptors: physiological significance and possible therapeutic applications. Phannacol. Rey (1998) 50(4): 597–664.
  • •Excellent review on glycine and NMDA receptors.
  • SMITH KE, BORDEN LA, HARTIG PR, BRANCHEK T, WEINSHANK RL: Cloning and expression of a glycine transporter reveal colocalization with NMDA receptors. Neuron (1992) 8(5):927–935.
  • ••Based on the expression of cloned GlyT1, this is the first suggestion that this transporter may monitor NMDA receptor activity in rat forebrain.
  • BOROWSKY B, MEZEY E, HOFFMAN BJ: Two glycine transporter variants with distinct localization in the CNS and peripheral tissues are encoded by a common gene. Neuron (1993) 10(5):851–863.
  • •First report on the existence of G1yT1 variants.
  • LIU QR, LOPEZ-CORCUERA B, MANDIYAN S, NELSON H, NELSON N: Cloning and expression of a spinal cord- and brain-specific glycine transporter with novel structural features. J. Biol. Chem. (1993) 268(30):22802–22808.
  • KIM KM, KINGSMORE SF, HAN H et al: Cloning of the human glycine transporter Type 1: molecular and pharmacological characterization of novel Expert Op/n. Investig. Drugs (2004) 13(5)519 isoform variants and chromosomal localization of the gene. Mol Pharmacol (1994) 45(4):608–617.
  • MORROW JA, COLLIE IT, DUNBAR DR, WALKER GB, SHAHID M, HILL DR: Molecular cloning and functional expression of the human glycine transporter G1yT2 and chromosomal localisation of the gene in the human genome. FEBS Lett. (1998) 439(3):334–340.
  • NELSON N: The family of Na+/C1-neurotransmitter transporters. .1. Neurochem. (1998) 71(5):1785–1803.
  • ZAFRA F, GOMEZA J, OLIVARES L, ARAGON C, GIMENEZ C: Regional distribution and developmental variation of the glycine transporters GLYT1 and GLYT2 in the rat CNS. Ear: Neurosci. (1995) 7(6):1342–1352.
  • ZAFRA F, ARAGON C, OLIVARES L, DANBOLT NC, GIMENEZ C, STORM-MATHISEN J: Glycine transporters are differentially expressed among CNS cells. Neurosci (1995) 15(5Pt. 2):3952–3969.
  • ••An elegant study demonstrating thedifferent cellular and subcellular localisation of G1yT1 and G1yT2.
  • SUPPLISSON S, BERGMAN C: Control of NMDA receptor activation by a glycine transporter co-expressed in Xenopus oocytes. Neurosci. (1997) 17(12):4580–4590.
  • ATKINSON BN, BELL SC, DE VIVO M et al.: ALX 5407: a potent, selective inhibitor of the hGlyT1 glycine transporter. Pharmacol (2001) 60(6):1414–1420.
  • ••Pharmacological characterisation of thefirst selective and potent G1yT1 inhibitor described.
  • AUBREY KR, VANDENBERG RJ: N- [3-(4'-fluorophenyl) 3 (4' phenylphenoxy)propyllsarcosine (NFPS) is a selective persistent inhibitor of glycine transport. Br. Pharmacol (2001) 134(7):1429–1436.
  • •Description of NFPS, published around the same time as [15].
  • MALLORGA PJ, WILLIAMS JB, JACOBSON M et al.: Pharmacology and expression analysis of glycine transporter G1yT1 with [3F1]- (N- [3-(4'-fluoropheny1)-3- (4'phenylphenoxy)propylBsarcosine. Neuropharmacology(2003) 45(5):585–593.
  • BERGER AJ, DIEUDONNE S, ASCHER P: Glycine uptake governs glycine site occupancy at NMDA receptors of excitatory synapses. I Neurophysiol (1998) 80(6):3336–3340.
  • ••Suggested that glycine re-uptake inhibitioncan modulate NMDA receptor activity.
  • KINNEY GG, SUR C, BURNO M et al: The glycine transporter Type 1 inhibitor N- [3-(4'-fluoropheny0-3-(4'-phenylphenoxy) propyllsarcosine potentiates NMDA receptor-mediated responses in vivo and produces an antipsychotic profile in rodent behavior. Neurosci. (2003) 23(20):7586–7591.
  • ••In vivo studies demonstrating that NFPScan potentiate NMDA receptor function and potentiate prepulse inhibition in vivo.
  • CHEN L, MUHLHAUSER M, YANG CR: Glycine tranporter-1 blockade potentiates NMDA-mediated responses in rat prefrontal cortical neurons in vitro and in vivo. .1. Neurophysiol (2003) 89(2):691–703.
  • •Interesting series of experiments showing that systemic NFPS can augment NMDA-induced cellular activity in the prefrontal cortex of rodents in vivo.
  • JAVITT DC, ZUKIN SR: Recent advances in the phencyclidine model of schizophrenia. Am. Psychiatry (1991) 148(10):1301–1308.
  • MILLAN MJ: N-methyl-D-aspartate receptor-coupled glycineB receptors in the pathogenesis and treatment of schizophrenia: a critical review. Cum Drug. Target CNS Nemo]. Disord. (2002) 1(2):191–213.
  • OLNEY JW, NEWCOMER JW, FARBER NB: NMDA receptor hypofunction model of schizophrenia. Psychiam. Res. (1999) 33(6):523–533.
  • TOTH E, LAJTHA A: Antagonism of phencyclidine-induced hyperactivity by glycine in mice. Neurochem. Res. (1986) 11(3)393–400.
  • JAVITT DC, SERSHEN H, HASHIM A, LAJTHA A: Reversal of phencyclidine-induced hyperactivity by glycine and the glycine uptake inhibitor glycyldodecylamide. Neuropsychopharmacology (1997) 17(3):202–204.
  • MeCAUGHRAN J, MAHJUBI E, DECENA E, HITZEMANN R: Genetics, haloperidol-induced catalepsy and haloperidol-induced changes in acoustic startle and prepulse inhibition. Psychopharmacology (1997) 134(2):131–139.
  • KLITENICK MA, ATKINSON BN, BAKER DA et al.: Development and characterization of GlyT1-selective glycine reuptake inhibitors. American College of Neuropsychopharmacology 40th Annual Meeting. Waikoloa, Hawaii (2001).
  • LE PEN G, KEW J, ALBERATI D, BORRONI E, HEITZ MP, MOREAU JL: Prepulse inhibition deficits of the startle reflex in neonatal ventral hippocampal-lesioned rats: reversal by glycine and a glycine transporter inhibitor. Biol. Psychiatry (2003) 54(11):1162–1170.
  • •Demonstration that glycine and a G1yT1 inhibitor enhances prepulse inhibition in a developmental animal model of schizophrenia.
  • LIPSKA BK, WEINBERGER DR: Delayed effects of neonatal hippocampal damage on haloperidol-induced catalepsy and apomorphine-induced stereotypic behaviors in the rat. Biafra Res. Dev. Biafra Res. (1993) 75(2):213–222.
  • SUMIOSHI T, ANIL AE, JIN D, JAYATHILAKE K, LEE M, MELTZER HY: Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms. Int. Neuropsychopharmacol (2004) 7(1):1–8.
  • JAVITT DC, ZYLBERMAN I, ZUKIN SR, HERESCO-LEVY U, LINDENMAYER JP: Amelioration of negative symptoms in schizophrenia by glycine. Am. .1. Psychiatry (1994) 151(8):1234–1236.
  • HERESCO-LEVY U, JAVITT D, ERMILOV M, MORDEL C, HOROWITZ A, KELLY D: Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. Br. j Psychiatry (1996) 169(5):610–617
  • ••First clinical study with glycine adjuvanttherapy demonstrating an improvement in both negative symptoms and cognition in schizophrenic patients.
  • JAVITT DC, SILIPO G, CIENFUEGOS A et al.: Adjunctive high-dose glycine in the treatment of schizophrenia. hat. I Neuropsychopharmacol (2001) 4(4):385–391.
  • HERESCO-LEVY U, JAVITT DC, ERMILOV M, MORDEL C, SILIPO G, LICHTENSTEIN M: Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch. Gen. Psychiatry (1999) 56(1):29–36.
  • HERESCO-LEVY U, ERMILOV M, LICHTENBERG P, BAR G, JAVITT DC: High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Biol. Psychiatry (2004) 55(2):165–171.
  • TSAI G, LANE H, YOUNG PJ, LANE N, CHONG M: Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Biol. Psychiatry (2004) I55(5):452–456.
  • ••The first description of clinical efficacy with a G1yT1 inhibitor (sarcosine) in schizophrenia.
  • HARSING LG JR, GACSALYI I, SZABO G et al.: The glycine transporter-1 inhibitors NFPS and Org 24461: a pharmacological study. Pharmacol Biochem. Behav. (2003) 74(4):811–825.
  • •Study investigating the effect of G1yT1 inhibitors in different behavioral models.
  • DIDRIKSEN M, HERTEL P, MORK A: Antipsychotic potential of the GlyT-1 inhibitor NFPS. Society for Neuroscience 2002 Annual Meeting. Washington, DC (2002).
  • GORFINKEL Y, MARTINA M, SCHMIDT CJ, BERGERON R: Blockade of the glycine transporter Type 1 enhances hippocampal LTP Society for _Neuroscience 2003 Annual Meeting.Washington, DC (2003).
  • SCHWARTZ BL, HASHTROUDI S, HERTING RL, SCHWARTZ P, DEUTSCH SI: D-Cycloserine enhances implicit memory in Alzheimer patients. Neurology (1996) 46(2):420–424.
  • TSAI GE, FALK WE, GUNTHER J, COYLE JT: Improved cognition in Alzheimer's disease with short-term D-cycloserine treatment. Am. I Psychiatry (1999) 156(3):467–469.
  • GOMEZA J, HULSMANN S, OHNO K et al.: Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition. Neuron (2003) 40(10:785–796.
  • ••First complete characterisation of G1yT1knockout mice.
  • BILLUPS D, ATTWELL D: Active releaseof glycine or D-serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse. Eur. NeuroscL (2003) 18(11):2975–8290.
  • POW DV: Amino acids and their transporters in the retina. Neurochem. Int. (2001) 38(6):463–484.
  • BROWN A, CARLYLE I, CLARK J et al.: Discovery and SAR of org 24598-a selective glycine uptake inhibitor. Bioorg. Med. Chem. Lett. (2001) 11(15):2007–2009.
  • LOWE JA 3rd, DROZDA SE, FISHER K et al: [3H]-(A-NPTS, a radioligand for the Type 1 glycine transporter. Bioorg. Med. Chem. Lett. (2003) 13(7):1291–1292. Patents

Websites

  • ALLELIX NEUROSCIENCE INC., NPS ALLELIX CORP: W002066456 (2002).
  • THE GENERAL HOSPITAL CORPORATION: U56228875 (2001)

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.