Epilepsy Research
Volume 28, Issue 1 , Pages 51-61 , July 1997

Anticonvulsant properties of two GABA uptake inhibitors NNC 05-2045 and NNC 05-2090, not acting preferentially on GAT-1

  • Nils Ole Dalby

      Affiliations

    • Novo Nordisk, Health Care Discovery, Novo Nordisk Park, DK-2760 Måløv, Denmark
    • Corresponding Author InformationCorresponding author. Tel.: +45 44434636; fax: +45 44434596; e-mail: nod@novo.dk
    • ,
  • Christian Thomsen

      Affiliations

    • Novo Nordisk, Health Care Discovery, Novo Nordisk Park, DK-2760 Måløv, Denmark
    • ,
  • Anders Fink-Jensen

      Affiliations

    • Novo Nordisk, Health Care Discovery, Novo Nordisk Park, DK-2760 Måløv, Denmark
    • ,
  • Jane Lundbeck

      Affiliations

    • Novo Nordisk, Health Care Discovery, Novo Nordisk Park, DK-2760 Måløv, Denmark
    • ,
  • Birgitte Søkilde

      Affiliations

    • Novo Nordisk, Health Care Discovery, Novo Nordisk Park, DK-2760 Måløv, Denmark
    • ,
  • Chiu Ming Man

      Affiliations

    • Institute of Psychiatry, Department of Neurology, De Crespigny Park, Denmark Hill, London, UK
    • ,
  • Per Olaf Sørensen

      Affiliations

    • Novo Nordisk, Health Care Discovery, Novo Nordisk Park, DK-2760 Måløv, Denmark
    • ,
  • Brian Meldrum

      Affiliations

    • Institute of Psychiatry, Department of Neurology, De Crespigny Park, Denmark Hill, London, UK

Received 30 January 1997 ,Revised 18 April 1997 ,Accepted 23 April 1997.

References 

  1. Bauer JS, Lenders T, Bettig U, Elger C. Efficacy and tolerability of tiagabine—results of an add-on study in patients with refractory partial seizures. J Epilepsy. 1995;8:83–86
  2. Borden LA, Dhar TGM, Smith KE, Weinshank RL, Branchek TA, Gluchowski C. Tiagabine, SK and F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1. Eur J Pharmacol. 1994;269:219–224
  3. Borden LA, Smith KE, Gustafson EL, Branchek TA, Weinshank RL. Cloning and expression of a betaine/GABA transporter from human brain. J Neurochem. 1995;64:977–984
  4. Borden LA, Smith KE, Hartig PR, Branchek TA, Weinshank RL. Molecular heterogeneity of the γ-aminobutyric acid (GABA) transport system. J Biol Chem. 1992;267:21098–21104
  5. Borden LA, Smith KE, Vaysse PJ-J, Gustafson EL, Weinshank RL, Branchek TA. Re-evaluation of GABA transport in neuronal and glial cell cultures: Correlation of pharmacology and mRNA localization. Receptors Channels. 1995;3:129–146
  6. Braestrup C, Nielsen EB, Sonnewald U, Knutsen LJS, Andersen KE, Jansen JA, et al. (R)-N-(4,4-bis(3-methyl-2thienyl)but-3-en-1-yl)nipecotic acid (tiagabine) binds with high affinity to the brain GABA uptake carrier. J Neurochem. 1990;54:639–647
  7. Browning RA. The role of neurotransmitters in electroshock seizure models. In: Jobe PC, Laird II HE, editors. Neurotransmitters and Epilepsy. New Jersey: Humana Press, 1987:277–320.
  8. Church J, Davies SN, Lodge D. Phencyclidine/sigma receptor agonists: anticonvulsant properties due to N-methylaspartate (NMA) antagonism. In: Excitatory Amino Acid Transmission, New York: Alan R. Liss, 1987:115–118.
  9. Clark JA, Amara SG. Stable expression of a neuronal γ-aminobutyric-acid transporter, GAT-3, in mammalian-cells demonstrates unique pharmacological properties and ion dependence. Mol Pharmacol. 1994;46:550–557
  10. Clark JA, Deutch AY, Gallipoli PZ, Amara SG. Functional expression and CNS distribution of a beta-alanine sensitive neuronal GABA transporter. Neuron. 1992;9:337–348
  11. Dhar TB, La Tyagarajan S, Smith K, Branchek T, Weinshank R, Gluchowski C. Design, synthesis and evaluation of substituted triarylnipecotic acid-derivatives as GABA uptake inhibitors—identification of a ligand with moderate affinity and selectivity for the cloned human gaba transporter gat-3. J Med Chem. 1995;37:2334–2342
  12. Dalby NO, Nielsen EB. Comparison of the anticonvulsant profiles of tiagabine, lamotrigine, gabapentin and vigabatrin. Epilepsy Res. 1997;28:63–72
  13. Faingold CL, Marcinczyk MJ, Casebeer DJ, Randall ME, Arneric SP, Browning RA. GABA in the inferior colliculus plays a critical role in control of audiogenic seizures. Brain Res. 1994;640:40–47
  14. Fink–Jensen A, Suzdak PD, Swedberg MDB, Judge ME, Hansen L, Nielsen PG. The γ-aminobutyric acid (GABA) uptake inhibitor, tiagabine, increases extracellular brain levels of GABA in awake rats. Eur J Pharmacol. 1992;220:197–201
  15. Gale K. GABA in epilepsy: The pharmacological basis. Epilepsia. 1989;30:S1–S11
  16. Guastella J, Nelson N, Nelson H, Czyzyk L, Keynan S, Miedel MC, et al. Cloning and expression of a rat brain GABA transporter. Science. 1990;249:1303–1306
  17. Ikegaki N, Saito N, Hashima M, Tanaka C. Production of specific antibodies against GABA transporter subtypes (GAT1, GAT2, GAT3) and their application to immunocytochemistry. Mol Brain Res. 1994;26:47–54
  18. Kanner BI. Sodium-coupled neurotransmitter transport: Structure, function and regulation. J Exp Biol. 1994;196:237–249
  19. Laird HE, Jobe PC. The genetically epilepsy prone rat. In: Jobe PC, Laird II HE, editors. Neurotransmitters and Epilepsy. New Jersey: Humana Press, 1987:57–94.
  20. Litchfield JT, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther. 1949;96:99–113
  21. Liu Q-R, Lopez–Corcuera B, Mandiyan S, Nelson H, Nelson N. Molecular characterization of four pharmacologically distinct γ-aminobutyric acid transporters in mouse brain. J Biol Chem. 1993;268:2106–2112
  22. Lopez–Corcuera B, Liu Q-R, Mandiyan S, Nelson H, Nelson N. Expression of a mouse brain cDNA encoding novel γ-aminobutyric acid transporter. J Biol Chem. 1992;267:17491–17493
  23. McNamara JO, Bonhaus DW, Crain BJ, Gellman RL, Shin C. Biochemical and pharmacologic studies of neurotransmitters in the kindling model. In Jobe PC, Laird II HE, editors. Neurotransmitters and Epilepsy. New Jersey, Humana Press:1987:115–160.
  24. Meldrum BS. GABAergic mechanisms as treatment of epilepsy. Br J Clin Pharmacol. 1988;27:35–115
  25. Meldrum BS. Epilepsy and γ-aminobutyric acid-mediated inhibition. Int Rev Neurobiol. 1975;17:1–36
  26. Minelli A, DeBiasi S, Brecha NC, Zuccarello LV, Conti F. GAT-3, a high-affinity GABA plasma membrane transporter, is localized to astrocytic processes, and is not confined to the vicinity of GABAergic synapses in the cerebral cortex. J Neurosci. 1996;16:6255–6264
  27. Nielsen EB, Suzdak PD, Andersen KE, Knutsen LJS, Sonnewald U, Braestrup C. Characterization of tiagabine (NO-328), a new potent and selective GABA uptake inhibitor. Eur J Pharmacol. 1991;196:257–266
  28. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. New York: Academic Press, 1986.
  29. Pontecarvo MJ, Karbon EW, Goode S, Clissold DB, Borosky SA, Patch RJ, et al. Possible cerebroprotective and in vivo NMDA antagonis activities of sigma receptors. Br Res Bull. 1991;26:461–465
  30. Racine RJ. Modification of seizure activity by electrical stimulation: II Motor seizure. Electroencephal Clin Neurophysiol. 1972;32:281–294
  31. Richens A, Chadwick DW, Duncan JS, Dam M, Gram L, Mikkelsen M, et al. Adjunctive treatment of partial seizures with tiagabine: A placebo controlled trial. Epilepsy Res. 1995;21:37–42
  32. Schwark WS, Löscher W. Comparison of the anticonvulsant effects of two novel GABA uptake inhibitors and diazepam in amygdaloid kindled rats. Naunyn-Scmeideberg's Arch Pharmacol. 1985;329:367–371
  33. Smith S, Parvez N, Chapman A, Meldrum B. The γ-aminobutyric-acid uptake inhibitor, tiagabine, is anticonvulsant in 2 animal-models of reflex epilepsy. Eur J Pharmacol. 1995;273:259–265
  34. Suzdak PJ, Janssen JA. A review of the preclinical pharmacology of tiagabine—a potent and selective anticonvulsant gaba uptake inhibitor. Epilepsia. 1995;36:612–626
  35. Thomsen C, Sørensen PO, Egebjerg J. 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methoxyphenyl)-4-piperidinol, a novel subtype selective inhibitor of the mouse type II GABA transporter. Br J Pharmacol. 1997;120:983–985
  36. Yamauchi A, Uchida S, Kwon HM, Preston AS, Robey RB, Garcia-Perez A, et al. Cloning of a Na+ and Cl−-dependent betaine transporter that is regulated by hypertonicity. J Biol Chem. 1992;267:649–652

PII: S0920-1211(97)00033-8

Epilepsy Research
Volume 28, Issue 1 , Pages 51-61 , July 1997

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