Anticonvulsant activity of the glial-selective GABA uptake inhibitor, THPO

Wood, J. D.; Johnson, David; Krogsgaard‐Larsen, Povl; Schousboe, Arne

doi:10.1016/0028-3908(83)90275-7

Cited by 38 publications

(9 citation statements)

References 11 publications

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“…Starting 15 DIV, some cultures without added neurons were treated with GABA (10 µM; Wako) and/or a GABA-uptake inhibitor, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO; 10 µM; Wako) (Wood et al, 1983), for 4 h to 3 days, to test the direct effects of exogenous GABA on astrocyte morphology. A GABA A -receptor agonist, muscimol (30 µM; Wako), and a GABA Breceptor agonist, baclofen (30 µM; Wako), were also used to identify GABA-receptor subtypes involved in the morphological alteration.…”

Section: Drug Treatmentmentioning

confidence: 99%

Neuronal regulation of astrocyte morphology in vitro is mediated by GABAergic signaling

Matsutani

Yamamoto

1997

Glia

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Section: Drug Treatmentmentioning

confidence: 99%

Neuronal regulation of astrocyte morphology in vitro is mediated by GABAergic signaling

Matsutani

Yamamoto

1997

Glia

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“…The GABAergic system is believed to have an important role in the origin and spread of seizure activity (3). Anticonvulsant properties have been shown for compounds that act to reduce the uptake of GABA from the extracellular space (4)(5)(6), enhance the activity of the GABA-benzodiazapine receptor complex, and block the degradation of GABA by GABA transaminase (7)(8)(9). Vigabatrin (4-aminohex-5-enoic acid) is a highly specific inhibitor of GABA transaminase (10).…”

mentioning

confidence: 99%

Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo.

Rothman

Petroff

Behar

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

492

530

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Localized 'H NMR spectroscopy in conjunction with J editing was used to measure the concentration of -aminobutyric acid (GABA) in the occipital lobe of four control human volunteers and four epileptic volunteers who were receiving the drug vigabatrin. The GABA concentration measured in four nonepileptic subjects was 1.1 ± 0.1 #mol/cm3 of brain, which is in good agreement with previous values measured in surgicaly removed human cortex. A dosedependent elevation of GABA concentration was measured in patients receiving the GABA tra inhibitor vigabatrin, with the maximum measured level of 3.7 pmol/cm3 of brain measured at the highest dose (6 g per day) studied. 'H NMR measurements of GABA in those patients receiving GABA-elevating agents such as vigabatrin wiUl be of importance in establishing the relationship between seizure suppression and the concentration of brain GABA.

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“…This activity is more apt to be neuronal than glial: Although nipecotic acid inhibits both glial and neuronal GABA uptake, the evidence that neurons account for 90% of total GABA uptake (Schousboe et al 1983) suggests that the drug's behavioral actions are mediated by its alteration of neuronal uptake. This theoretical argument is bolstered by the empirical evidence that ethyl nipecotate, like other GABAergic agents, has potent antiepileptic effects which are only weakly reproduced by glia-specific uptake inhibitors like fl-alanine and THPO (Horton et al 1979;Wood et al 1983). It should be noted that the R and S isomers of ethyl nipecotate also reduce GAD and increase GABA-T activity, respectively (Frey et al 1979).…”

Section: Discussionmentioning

confidence: 98%

Differential effects of ethyl (R,S)-nipecotate on the behaviors of highly and minimally aggressive female golden hamsters

Potegal

1986

Psychopharmacology

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The GABA uptake inhibitor ethyl (R,S)-nipecotate produces a dose-dependent suppression of aggression in highly aggressive hamsters but not in minimally aggressive ones. This suppression occurs at doses below those producing peripheral cholinergic effects; at the highest dose used it persists after these effects have dissipated. Doses sufficient to suppress aggression have no significant effect on grooming, locomotor activity and other behaviors but do affect sunflower seed acceptance. The differential effects of the drug on highly and minimally aggressive animals may indicate that their differences in aggression are due to differences in endogenous GABAergic activity. These results, together with previous evidence for parallel circadian variation in GABA uptake and aggressive behavior, suggest that GABA uptake may be an important endogenous regulator of aggression.

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Anticonvulsant activity of the glial-selective GABA uptake inhibitor, THPO

Cited by 38 publications

References 11 publications

Neuronal regulation of astrocyte morphology in vitro is mediated by GABAergic signaling

Neuronal regulation of astrocyte morphology in vitro is mediated by GABAergic signaling

Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo.

Differential effects of ethyl (R,S)-nipecotate on the behaviors of highly and minimally aggressive female golden hamsters

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