GABA uptake inhibitor

Thompson, SM and Gahwiler, BH (1992) Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures. J. Neurophysiol. 67 1698-1701. 

N GokaV et al. (1991) GABA-uptake inhibitors construction of a general pharmacophore model and successful prediction of a new representative. J Med Chem 34(8) 2547-2557... 

GABA-A receptor ligands GABA uptake inhibitors... 

Krogsgaard-Larsen, P., Frplund, B., and Frydenvang, K. (2000) GABA uptake inhibitors. Design, molecular pharmacology and therapeutic aspects. Curr. Pharm. Des. 6, 1193-1209. 

Larsson, O. M., Falch, E., Schousboe, A., and Krogsgaard-Larsen, P. (1991) GABA uptake inhibitors Kinetics and molecular pharmacology, in Presynaptic Receptors, and Neuronal Transporters (Langer, S. Z., Galzin, A. M., and Costentin, J., eds.), Pergamon Press, Oxford, UK, pp. 197-200. 

Knutsen, L. J., Andersen, K. E., Lau, J., et al. (1999) Synthesis of novel GABA uptake inhibitors. 3. Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine as anticonvulsant agents. J. Med. Chem. 42, 3447-3462. 

Andersen, K. E Lau, J., Lundt, B. F Petersen, H Huusfeldt, P. 0., Suzdak, P. D., and Swedberg, M. D. (2001) Synthesis of novel GABA uptake inhibitors. Part 6 preparation and evaluation of N-Omega asymmetrically substituted nipecotic acid derivatives. Bioorg. Med. Chem. 9,2773-2785. 

Meldrum, B. S., Croucher, M. J., and Krogsgaard-Larsen, P. (1981) GABA-uptake inhibitors as anticonvulsant agents, in Problems in GABA Research From Brain to Bacteria (Okada, Y. and Roberts, E., eds.) Excerpta Medica, Amsterdam, pp. 182-191. 

Wood, J. D., Johnson, D. D., Krogsgaard-Larsen, P., and Schousboe, A. (1983) Anticonvulsant activity of the glial-selective GABA uptake inhibitor, THPO. Neuropharmacology 22, 139-142. 

The EEG effects of valerian are most concordant with those of tiagabine, a GABA uptake inhibitor used to treat epilepsy. Tiagabine also increases slow-wave sleep, but unlike valerian has little or no effect on REM (Lancel et al. 1998). GABAA agonists also tend to have this effect. 

Lancel M, Faulhaber J, Deisz RA. (1998). Effect of the GABA uptake inhibitor tiagabine on sleep and EEG power spectra in the rat. Br J Pharmacoi. 123(7) 1471-77. 

Of the many drugs that have been developed which modulate GABA function, the inhibitors of GABA transaminase have been shown to be effective anticonvulsants. These are derivatives of valproic acid that not only inhibit the metabolism of GABA but may also act as antagonists of the GABA autoreceptor and thereby enhance the release of the neurotransmitter. GABA-uptake inhibitors have also been developed (for example, derivatives... 

Zhao, X., Hoesl, C. E., Hoefher, G. C., Wanner, K. T. Synthesis and biological evaluation of new GABA-uptake inhibitors derived from proline and from pyrrolidme-2-acetic acid. Eur. J. Med. Chem. 2005, 40, 231-247. 

UDP-a-glucuronic acid 90 unbound drug concentration 50 unbound drug 24,125 GABA uptake inhibitors 6 histamine -receptor antagonists uptake of drugs in the brain 6 urea 42 urine 62, 67... 

GABA (y-aminobutyric acid) is a major neurotransmitter in mammals and is involved in various CNS disorders. In the design of a series of GABA uptake inhibitors a large difference in in vivo activity between two compounds with identical IC50 val-... 

Reincorporation of the tin can be avoided by using a tri wry/stannane precursor.156 This means that the product organolithium can be trapped with other electrophiles, provided that the solvent is 10 1 hexane-ether, and not THF, which otherwise protonates the product organolithium.157 The hexane-ether mixture slows down the tin-lithium exchange reaction dramatically, and it proceeds only at room temperature. Cyclisation of 323 thus leads to the synthesis of a simple GABA uptake inhibitor 324. A-acyl pyrrolidines cannot be made directly from a-amido organolithiums, as these fail to cyclise, possibly because they are too well stabilised by O-Li coordination.138... 

Nielsen EB, Sonnewald U, Sorensen PO, Suzdak PD, Knudsen L). The synthesis ofnovel GABA uptake inhibitors. 1. Elu-... 

Quandt G, Hofiter G, Wanner KT (2013) Synthesis and evaluation of N-substituted nipecotic acid derivatives with an unsymmet-rical bis-aromatic residue attached to a vinyl ether spacer as potential GABA uptake inhibitors. Bioorg Med Chem 21 3363-3378... 

GABA uptake inhibitors Kardos et alP Glycine antagonists Salituro et alP... 

Falch, E., Krogsgaard-Larsen, P. GABA uptake inhibitors. Syntheses and structure-activity studies on GABA analogues containing diaryl-butenyl and diarylmethoxyalkyl V-substituents. Eur. J. Med. Chem. 1991,26, 69-78. 

Krogsgaard-Larsen P, Frolund B, Frydenvang K GABA uptake inhibitors Design, molecular pharma-... 

Andersen, K.E., Braestmp, C., Groenwald, F.C., Joergensen, A.S., Nielsen, E.B., etal. The synthesis of novel GABA uptake inhibitors. 1. Elucidation of the strucmre-activity studies leading to the choice of (R)-l.[4,4-Bis(3-methyl-2-thienyl>3-butenyl]-3-piperidinecarboxylic acid (Tiagabine) as an anticonvulsant drug candidate. J. Med. Chem. 36 1716-1725. 

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