[3H]Nipecotic acid binding to GABA uptake sites in human brain

1992 ◽  
Vol 580 (1-2) ◽  
pp. 311-316 ◽  
Author(s):  
Ingrid Sundman ◽  
Ulrika Lernmark ◽  
Jan Marcusson
Keyword(s):  
Human Brain ◽  
Gaba Uptake ◽  
Nipecotic Acid ◽  
Uptake Sites

[3H]Tiagabine binding to GABA uptake sites in human brain

1999 ◽  
Vol 851 (1-2) ◽  
pp. 183-188 ◽  
Author(s):  
Ingrid Sundman Eriksson ◽  
Per Allard ◽  
Jan Marcusson
Keyword(s):  
Human Brain ◽  
Gaba Uptake ◽  
Uptake Sites

scholarly journals Design, Synthesis and Enhanced BBB Penetration Studies of L-serine-Tethered Nipecotic Acid-Prodrug

Drug Research ◽  
2020 ◽  
Author(s):  
Meenakshi Dhanawat ◽  
Sumeet Gupta ◽  
Dinesh Kumar Mehta ◽  
Rina Das
Keyword(s):  
Epileptic Activity ◽  
Aminobutyric Acid ◽  
Gaba Uptake ◽  
Nipecotic Acid ◽  
Design Synthesis ◽  
Hydrophilic Nature ◽  
Carrier Mediated Transport ◽  
Ester Prodrug ◽  
Hplc Data

Nipecotic acid is considered to be one of the most potent inhibitors of neuronal and glial-aminobutyric acid (GABA) uptake in vitro. Due to its hydrophilic nature, nipecotic acid does not readily cross the blood-brain barrier (BBB). Large neutral amino acids (LAT1)-knotted nipecotic acid prodrug was designed and synthesized with the aim to enhance the BBB permeation by the use of carrier-mediated transport. The synthesized prodrug was tested in animal models of Pentylenetetrazole (PTZ)-induced convulsions in mice. Further pain studies were carried out followed by neurotoxicity estimation by writhing and rota-rod test respectively. HPLC data suggests that the synthesized prodrug has improved penetration through BBB. Nipecotic acid-L-serine ester prodrug with considerable anti-epileptic activity, and the ability to permeate the BBB has been successfully synthesized. Graphical Abstract.

Systemic CI-966, a new γ-aminobutyric acid uptake blocker, enhances γ-aminobutyric acid action in CA1 pyramidal layer in situ

1990 ◽  
Vol 68 (9) ◽  
pp. 1194-1199 ◽  
Author(s):  
U. Ebert ◽  
K. Krnjević
Keyword(s):  
Aminobutyric Acid ◽  
Gaba Uptake ◽  
Acid Uptake ◽  
Sprague Dawley ◽  
Nipecotic Acid ◽  
Ca1 Region ◽  
Stratum Pyramidale ◽  
Sprague Dawley Rats ◽  
Pyramidal Layer ◽  
Urethane Anaesthesia

A new potent, blood–brain barrier permeable γ-aminobutyric acid (GABA) uptake blocker, 1-[2-[bis[4-(trifluoromethyl)-phenyl]methoxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid (CI-966) was administered systemically by i.p. injection (5 mg/kg) in Sprague–Dawley rats under urethane anaesthesia. Twenty to thirty minutes after injection there was a highly variable, but overall significant, enhancement of the inhibition of hippocampal population spikes by GABA applied by microiontophoresis in the CA1 region. Like the effect of nipecotic acid (applied locally by iontophoresis), the potentiation by CI-966 was clearest when GABA was applied in or near the stratum pyramidale where its action normally is weakest and shows the most pronounced fading. This change in GABA potency is most simply explained by a reduction in GABA uptake.Key words: GABA, muscimol, nipecotic acid, GABA-uptake blocker, epilepsy.

GAT-1 and Reversible GABA Transport in Bergmann Glia in Slices

2002 ◽  
Vol 88 (3) ◽  
pp. 1407-1419 ◽  
Author(s):  
L. Barakat ◽  
A. Bordey
Keyword(s):  
Gaba Receptors ◽  
Receptor Activation ◽  
Bergmann Glia ◽  
Gaba Uptake ◽  
Induced Voltage ◽  
Nipecotic Acid ◽  
Gaba Transporters ◽  
Whole Cell Patch Clamp ◽  
Inward Currents

Although glial GABA uptake and release have been studied in vitro, GABA transporters (GATs) have not been characterized in glia in slices. Whole cell patch-clamp recordings were obtained from Bergmann glia in rat cerebellar slices to characterize carrier-mediated GABA influx and efflux. GABA induced inward currents at −70 mV that could be pharmacologically separated into GABAA receptor and GAT currents. In the presence of GABAA/B/C receptor blockers, mean GABA-induced currents measured −48 pA at −70 mV, were inwardly rectifying between −70 and +50 mV, were inhibited by external Na+ removal, and were diminished by reduction of external Cl−. Nontransportable blockers of GAT-1 (SKF89976-A and NNC-711) and a transportable blocker of all the GAT subtypes (nipecotic acid) reversibly reduced GABA-induced transport currents by 68 and 100%, respectively. A blocker of BGT-1 (betaine) had no effect. SKF89976-A and NNC-711 also suppressed baseline inward currents that likely result from tonic GAT activation by background GABA. The substrate agonists, nipecotic acid and β-alanine but not betaine, induced voltage- and Na+-dependent currents. With Na+ and GABA inside the patch pipette or intracellular GABA perfusion during the recording, SKF89976-A blocked baseline outward currents that activated at −60 mV and increased with more depolarized potentials. This carrier-mediated GABA efflux induced a local accumulation of extracellular GABA detected by GABAA receptor activation on the recorded cell. Overall, these results indicate that Bergmann glia express GAT-1 that are activated by ambient GABA. In addition, GAT-1 in glia can work in reverse and release sufficient GABA to activate nearby GABA receptors.

[3H]GBR-12935 binding to dopamine uptake sites in the human brain

1988 ◽  
Vol 457 (1) ◽  
pp. 122-129 ◽  
Author(s):  
Jan Marcusson ◽  
Kristina Eriksson
Keyword(s):  
Human Brain ◽  
Dopamine Uptake ◽  
Dopamine Uptake Sites ◽  
Uptake Sites

The interaction of antidepressant drugs with neurotransmitter receptor bidning sites and 5-HT uptake sites in human brain in vitro

1993 ◽  
Vol 3 (3) ◽  
pp. 344-345 ◽  
Author(s):  
R.W. Horton ◽  
F. De Paermentier ◽  
S. Lowther ◽  
K.M. Lawrence ◽  
M.R. Crompton ◽  
...  
Keyword(s):  
Human Brain ◽  
Antidepressant Drugs ◽  
Neurotransmitter Receptor ◽  
Uptake Sites ◽  
5 Ht Uptake

Synthesis of analogues of GABA. VIII. Selective a-alkylation and γ-halogenation of the dianion from α,β-unsaturated nipecotic acid derivatives

1983 ◽  
Vol 36 (3) ◽  
pp. 601 ◽  
Author(s):  
RD Allan ◽  
J Fong
Keyword(s):  
Amino Acid ◽  
Carboxylic Acid ◽  
Alkylating Agents ◽  
Gaba Uptake ◽  
Nipecotic Acid ◽  
Uptake Inhibitor ◽  
Gaba Uptake Inhibitor ◽  
Unsaturated Amino Acid

1,2,3,6-Tetrahydropyridine-3-carboxylic acid (3), the β, γ-unsaturated derivative of the GABA uptake inhibitor nipecotic acid (1), has been synthesized by deconjugation via the dilithium salt of the N-t-butyloxycarbonyl-protected intermediate (6). Substitution of the intermediate with alkylating agents or an aldehyde gave predominantly a-alkylated products but chlorination with N-chlorosuccinimide provided a route to the γ-substituted unsaturated amino acid (13a).

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