Structure-Activity Relationship and Pharmacology of γ-Aminobutyric Acid (GABA) Transport Inhibitors

Advances in Pharmacology

Volumn 54, Issue , 2006, Pages 265-284

  Clausen, Rasmus Prætorius ^a   Madsen, Karsten ^a   Larsson, Orla Miller ^a   Frølund, Bente ^a   Krogsgaard Larsen, Povl ^a   Schousboe, Arne ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

1 [2 (BENZHYDRYLIDENEAMINOOXY)ETHYL] 1,2,5,6 TETRAHYDRO 3 PYRIDINECARBOXYLIC ACID; 4 AMINOBUTYRIC ACID CARRIER; 4 AMINOBUTYRIC ACID RECEPTOR BLOCKING AGENT; 4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; NEUROTRANSMITTER UPTAKE INHIBITOR; NIPECOTIC ACID DERIVATIVE; OXIME; TIAGABINE;

ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; DRUG ANTAGONISM; HUMAN; METABOLISM; REVIEW; STRUCTURE ACTIVITY RELATION;

ANIMALS; GABA AGONISTS; GABA ANTAGONISTS; GABA PLASMA MEMBRANE TRANSPORT PROTEINS; HUMANS; MOLECULAR STRUCTURE; NEUROTRANSMITTER UPTAKE INHIBITORS; NIPECOTIC ACIDS; OXIMES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33744462712     PISSN: 10543589     EISSN: None     Source Type: Book Series    
DOI: 10.1016/S1054-3589(06)54011-6     Document Type: Review

References (55)

1. A receptors characterized by fluorescence resonance energy transfer-derived measurements of membrane potential. J. Biol. Chem. 276 42 (2001) 38934-38939
2. Ali F.E., Bondinell W.E., Dandridge P.A., Frazee J.S., Garvey E., Girard G.R., Kaiser C., Ku T.W., Lafferty J.J., and Moonsammy G.I. Orally active and potent inhibitors of gamma-aminobutyric acid uptake. J. Med. Chem. 28 5 (1985) 653-660
3. Andersen K.E., Braestrup C., Gronwald F.C., Jørgensen A.S., Nielsen E.B., Sonnewald U., Sørensen P.O., Suzdak P.D., and Knutsen L.J. The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the structure-activity studies leading to the choice of (R)-1-[4,4-bis(3-methyl-2-thienyl)-3-butenyl]-3-piperidinecarboxylic acid (tiagabine) as an anticonvulsant drug candidate. J. Med. Chem. 36 12 (1993) 1716-1725
4. Andersen K.E., Begtrup M., Chorghade M.S., Lee E.C., Lau J., Lundt B.F., Petersen H., Sørensen P.O., and Thøgersen H. The synthesis of novel GABA uptake inhibitors. 2. Synthesis of 5-hydroxytiagabine, a human metabolite of the GABA reuptake inhibitor Tiagabine. Tetrahedron 50 29 (1994) 8699-8710
5. Andersen K.E., Sørensen J.L., Huusfeldt P.O., Knutsen L.J., Lau J., Lundt B.F., Petersen H., Suzdak P.D., and Swedberg M.D. Synthesis of novel GABA uptake inhibitors. 4. Bioisosteric transformation and successive optimization of known GABA uptake inhibitors leading to a series of potent anticonvulsant drug candidates. J. Med. Chem. 42 21 (1999) 4281-4291
6. Andersen K.E., Sørensen J.L., Lau J., Lundt B.F., Petersen H., Huusfeldt P.O., Suzdak P.D., and Swedberg M.D. Synthesis of novel γ-aminobutyric acid (GABA) uptake inhibitors. 5. Preparation and structure-activity studies of tricyclic analogues of known GABA uptake inhibitors. J. Med. Chem. 44 13 (2001) 2152-2163
7. Andersen K.E., Lau J., Lundt B.F., Petersen H., Huusfeldt P.O., Suzdak P.D., and Swedberg M.D.B. Synthesis of novel GABA uptake inhibitors. Part 6: Preparation and evaluation of N-O asymmetrically substituted nipecotic acid derivatives. Bioorg. Med. Chem. 9 11 (2001) 2773-2785
8. Bismuth Y., Kavanaugh M.P., and Kanner B.I. Tyrosine 140 of the γ-aminobutyric acid transporter GAT-1 plays a critical role in neurotransmitter recognition. J. Biol. Chem. 272 26 (1997) 16096-16102
9. Bolvig T., Larsson O.M., Pickering D.S., Nelson N., Falch E., Krogsgaard-Larsen P., and Schousboe A. Action of bicyclic isoxazole GABA analogues on GABA transporters and its relation to anticonvulsant activity. Eur. J. Pharmacol. 375 (1999) 367-374
10. Borden L.A. GABA transporter heterogeneity: Pharmacology and cellular localization. Neurochem. Int. 29 4 (1996) 335-356
11. Borden L.A., Smith K.E., Hartig P.R., Branchek T.A., and Weinshank R.L. Molecular heterogeneity of the γ-aminobutyric acid (GABA) transport system. Cloning of two novel high affinity GABA transporters from rat brain. J. Biol. Chem. 267 29 (1992) 21098-21104
12. Borden L.A., Murali Dhar T.G., Smith K.E., Weinshank R.L., Branchek T.A., and Gluchowski C. Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1. Eur. J. Pharmacol. 269 2 (1994) 219-224
13. Borden L.A., Smith K.E., Vaysse P.J., Gustafson E.L., Weinshank R.L., and Branchek T.A. Re-evaluation of GABA transport in neuronal and glial cell cultures: Correlation of pharmacology and mRNA localization. Receptors Channels 3 (1995) 129-146
14. Braestrup C., Nielsen E.B., Sonnewald U., Knutsen L.J.S., Andersen K.E., Jansen J.A., Frederiksen K., Andersen P.H., Mortensen A., and Suzdak P.D. (R)-N-[4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid binds with high-affinity to the brain γ-aminobutyric acid uptake carrier. J. Neurochem. 54 2 (1990) 639-647
15. Clausen R.P., Moltzen E.K., Perregaard J., Lenz S.M., Sanchez C., Falch E., Frolund B., Bolvig T., Sarup A., and Larsson O.M. Selective inhibitors of GABA uptake: Synthesis and molecular pharmacology of 4-N-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol analogues. Bioorg. Med. Chem. 13 3 (2005) 895-908
16. Conti F., Melone M., De Biasi S., Minelli A., Brecha N.C., and Ducati A. Neuronal and glial localization of GAT-1, a high-affinity γ-aminobutyric acid plasma membrane transporter, in human cerebral cortex: With a note on its distribution in monkey cortex. J. Comp. Neurol. 396 1 (1998) 51-63
17. Conti F., Zuccarello L.V., Barbaresi P., Minelli A., Brecha N.C., and Melone M. Neuronal, glial, and epithelial localization of γ-aminobutyric acid transporter 2, a high-affinity gamma-aminobutyric acid plasma membrane transporter, in the cerebral cortex and neighboring structures. J. Comp. Neurol. 409 3 (1999) 482-494
18. Conti F., Minelli A., and Melone M. GABA transporters in the mammalian cerebral cortex: Localization, development and pathological implications. Brain Res. Brain Res. Rev. 45 3 (2004) 196-212
19. Dhar T.G., Borden L.A., Tyagarajan S., Smith K.E., Branchek T.A., Weinshank R.L., and 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. 37 15 (1994) 2334-2342
20. Durkin M.M., Smith K.E., Borden L.A., Weinshank R.L., Branchek T.A., and Gustafson E.L. Localization of messenger RNAs encoding three GABA transporters in rat brain: An in situ hybridization study. Brain Res. Mol. Brain Res. 33 1 (1995) 7-21
21. Falch E., Perregaard J., Frølund B., Søkilde B., Buur A., Hansen L.M., Frydenvang K., Brehm L., Bolvig T., Larsson O.M., Sanchez C., White H.S., et al. Selective inhibitors of glial GABA uptake: Synthesis, absolute stereochemistry, and pharmacology of the enantiomers of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole (exo-THPO) and analogues. J. Med. Chem. 42 26 (1999) 5402-5414
22. Guastella J., Nelson N., Nelson H., Czyzyk L., Keynan S., Miedel M.C., Davidson N., Lester H.A., and Kanner B.I. Cloning and expression of a rat brain GABA transporter. Science 249 (1990) 1303-1306
23. Hertz E., Yu A.C.H., Hertz L., Juurlink B.H.J., and Schousboe A. Preparation of primary cultures of mouse cortical neurons. In: Shahar A., de Vellis J., Vernadakis A., and Haber B. (Eds). "A Dissection and Tissue Culture Manual of the Nervous System" (1989), Alan R. Liss, Inc., New York 183-186
24. Hertz L., Juurlink B.H.J., Fosmark H., and Schousboe A. Astrocytes in primary cultures. In: Pfeiffer S.E. (Ed). "Neuroscience Approached Through Cell Culture" (1982), CRC Press, Boca Raton, Florida 175-186
25. Hertz L., Juurlink B.H.J., Hertz E., Fosmark H., and Schousboe A. Preparation of primary cultures of mouse (rat) astrocytes. In: Shahar A., de Vellis J., Vernadakis A., and Haber B. (Eds). "A Dissection and Tissue Culture Manual of the Nervous System" (1989), Alan R. Liss, Inc., New York 105-108
26. Iversen L.L., and Kelly J.S. Uptake and metabolism of γ-aminobutyric acid by neurons and glial cells. Biochem. Pharmacol. 24 9 (1975) 933-938
27. 3H]GABA by slices of rat cerebral cortex. J. Neurochem. 15 10 (1968) 1141-1149
28. Knutsen L.J., Andersen K.E., Lau J., Lundt B.F., Henry R.F., Morton H.E., Naerum L., Petersen H., Stephensen H., Suzdak P.D., Swedberg M.D., Thomsen C., and Sørensen P.O. Synthesis of novel GABA uptake inhibitors. 3. Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine as anticonvulsant agents. J. Med. Chem. 42 18 (1999) 3447-3462
29. Krogsgaard-Larsen P., and Johnston G.A.R. Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxazoles and related compounds. J. Neurochem. 25 6 (1975) 797-802
30. Krogsgaard-Larsen P., Johnston G.A.R., Curtis D.R., Game C.J., and McCulloch R.M. Structure and biological activity of a series of conformationally restricted analogues of GABA. J. Neurochem. 25 6 (1975) 803-809
31. Krogsgaard-Larsen P., Mikkelsen H., Jacobsen P., Falch E., Curtis D.R., Peet M.J., and Leah J.D. 4,5,6,7-Tetrahydroisothiazolo[5,4-c]pyridin-3-ol and related analogues of THIP. Synthesis and biological activity. J. Med. Chem. 26 6 (1983) 895-900
32. Krogsgaard-Larsen P., Frølund B., and Frydenvang K. GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects. Curr. Pharm. Des. 6 12 (2000) 1193-1209
33. Larsson O.M., Thorbek P., Krogsgaard-Larsen P., and Schousboe A. Effect of homo-beta-proline and other heterocyclic GABA analogues on GABA uptake in neurons and astroglial cells and on GABA receptor binding. J. Neurochem. 37 (1981) 1509-1516
34. Larsson O.M., Johnston G.A., and Schousboe A. Differences in uptake kinetics of cis-3-aminocyclohexane carboxylic acid into neurons and astrocytes in primary cultures. Brain Res. 260 (1983) 279-285
35. Larsson O.M., Falch E., Krogsgaard-Larsen P., and Schousboe A. Kinetic characterization of inhibition of γ-aminobutyric acid uptake into cultured neurons and astrocytes by 4,4-diphenyl-3-butenyl derivatives of nipecotic acid and guvacine. J. Neurochem. 50 3 (1988) 818-823
36. Lloyd K.G., and Morselli P.L. Psychopharmacology of GABAergic drugs. In: Meltzer H.Y. (Ed). "Psychopharmacology: The Third Generation of Progress" (1987), Raven Press, New York 183-195
37. Minelli A., DeBiasi S., Brecha N.C., Zuccarello L.V., and Conti F. GAT-3, a high-affinity GABA plasma membrane transporter, is localized to astrocytic processes, and it is not confined to the vicinity of GABAergic synapses in the cerebral cortex. J. Neurosci. 16 19 (1996) 6255-6264
38. Neal M.J., and Bowery N.G. Cis-3-aminocyclohexanecarboxylic acid: A substrate for the neuronal GABA transport system. Brain Res. 138 1 (1977) 169-174
39. Pavia M.R., Lobbestael S.J., Nugiel D., Mayhugh D.R., Gregor V.E., Taylor C.P., Schwarz R.D., Brahce L., and Vartanian M.G. Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake. J. Med. Chem. 35 22 (1992) 4238-4248
40. Pietrini G., Suh Y.J., Edelmann L., Rudnick G., and Caplan M.J. The axonal gamma-aminobutyric acid transporter GAT-1 is sorted to the apical membranes of polarized epithelial cells. J. Biol. Chem. 269 6 (1994) 4668-4674
41. Radian R., Ottersen O.P., Storm-Mathisen J., Castel M., and Kanner B.I. Immunocytochemical localization of the GABA transporter in rat brain. J. Neurosci. 10 4 (1990) 1319-1330
42. Sarup A., Larsson O.M., Bolvig T., Frølund B., Krogsgaard-Larsen P., and Schousboe A. Effects of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazol (exo-THPO) and its N-substituted analogs on GABA transport in cultured neurons and astrocytes and by the four cloned mouse GABA transporters. Neurochem. Int. 43 4-5 (2003) 445-451
43. Schousboe A., and Kanner B.I. GABA transporters: Functional and pharmacological properties. In: Egebjerg J., Schousboe A., and Krogsgaard-Larsen P. (Eds). "Glutamate and GABA Receptors and Transporters: Structure, Function and Pharmacology" (2002), Taylor and Francis, London 337-349
44. Schousboe A., Krogsgaard-Larsen P., Svenneby G., and Hertz L. Inhibition of the high-affinity, net uptake of GABA into cultured astrocytes by beta-proline, nipecotic acid and other compounds. Brain Res. 153 (1978) 623-626
45. Schousboe A., Thorbek P., Hertz L., and Krogsgaard-Larsen P. Effects of GABA analogues of restricted conformation on GABA transport in astrocytes and brain cortex slices and on GABA receptor binding. J. Neurochem. 33 (1979) 181-189
46. Schousboe A., Larsson O.M., Wood J.D., and Krogsgaard-Larsen P. Transport and metabolism of γ-aminobutyric acid in neurons and glia: Implications for epilepsy. Epilepsia 24 5 (1983) 531-538
47. Schousboe A., Sarup A., Bak L.K., Waagepetersen H.S., and Larsson O.M. Role of astrocytic transport processes in glutamatergic and GABAergic neurotransmission. Neurochem. Int. 45 4 (2004) 521-527
48. Thomsen C., Sørensen P.O., and 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. 120 6 (1997) 983-985
49. Todorov A.A., Kolchev C.B., and Todorov A.B. Tiagabine and gabapentin for the management of chronic pain. Clin. J. Pain 21 4 (2005) 358-361
50. Waagepetersen H.S., Sonnewald U., and Schousboe A. Compartmentation of glutamine, glutamate, and GABA metabolism in neurons and astrocytes: Functional implications. Neuroscientist 9 5 (2003) 398-403
51. White H.S., Sarup A., Bolvig T., Kristensen A.S., Petersen G., Nelson N., Pickering D.S., Larsson O.M., Frølund B., Krogsgaard-Larsen P., and Schousboe A. Correlation between anticonvulsant activity and inhibitory action on glial γ-aminobutyric acid uptake of the highly selective mouse γ-aminobutyric acid transporter 1 inhibitor 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole and its N-alkylated analogs. J. Pharmacol. Exp. Ther. 302 2 (2002) 636-644
52. White H.S., Watson W.P., Hansen S.L., Slough S., Perregaard J., Sarup A., Bolvig T., Petersen G., Larsson O.M., Clausen R.P., Frølund B., Falch E., et al. First demonstration of a functional role for central nervous system betaine/γ-aminobutyric acid transporter (mGAT2) based on synergistic anticonvulsant action among inhibitors of mGAT1 and mGAT2. J. Pharmacol. Exp. Ther. 312 2 (2005) 866-874
53. Yunger L.M., Fowler P.J., Zarevics P., and Setler P.E. Novel inhibitors of γ-aminobutyric acid (GABA) uptake: Anticonvulsant actions in rats and mice. J. Pharmacol. Exp. Ther. 228 1 (1984) 109-115
54. Zhu X.M., and Ong W.Y. A light and electron microscopic study of betaine/GABA transporter distribution in the monkey cerebral neocortex and hippocampus. J. Neurocytol. 33 2 (2004) 233-240
55. Zwanzger P., and Rupprecht R. Selective GABAergic treatment for panic? Investigations in experimental panic induction and panic disorder. J. Psychiatry Neurosci. 30 3 (2005) 167-175