CDC20siRNA and paclitaxel co-loaded nanometric liposomes of a nipecotic acid-derived cationic amphiphile inhibit xenografted neuroblastoma

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.

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Structural, spectroscopic and computational studies of the 2:1 complex of nipecotic acid with squaric acid

Chemical Physics ◽

10.1016/j.chemphys.2014.09.004 ◽

2014 ◽

Vol 444 ◽

pp. 7-14 ◽

Cited By ~ 6

Author(s):

Elżbieta Bartoszak-Adamska ◽

Zofia Dega-Szafran ◽

Anna Komasa ◽

Mirosław Szafran

Keyword(s):

Squaric Acid ◽

Computational Studies ◽

Nipecotic Acid

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

Brain Research ◽

10.1016/0006-8993(92)90959-d ◽

1992 ◽

Vol 580 (1-2) ◽

pp. 311-316 ◽

Cited By ~ 5

Author(s):

Ingrid Sundman ◽

Ulrika Lernmark ◽

Jan Marcusson

Keyword(s):

Human Brain ◽

Gaba Uptake ◽

Nipecotic Acid ◽

Uptake Sites

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Design, synthesis, characterization, and molecular modeling studies of novel oxadiazole derivatives of nipecotic acid as potential anticonvulsant and antidepressant agents

Medicinal Chemistry Research ◽

10.1007/s00044-017-2047-y ◽

2017 ◽

Vol 27 (1) ◽

pp. 137-152 ◽

Cited By ~ 4

Author(s):

Ravi Bhushan Singh ◽

Gireesh Kumar Singh ◽

Krishna Chaturvedi ◽

Devendra Kumar ◽

Sushil Kumar Singh ◽

...

Keyword(s):

Molecular Modeling ◽

Nipecotic Acid ◽

Design Synthesis ◽

Antidepressant Agents ◽

Modeling Studies ◽

Oxadiazole Derivatives ◽

Molecular Modeling Studies ◽

Derivatives Of

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Chiral separation of nipecotic acid amides

Journal of Chromatography A ◽

10.1016/0021-9673(92)80162-n ◽

1992 ◽

Vol 609 (1-2) ◽

pp. 187-193 ◽

Cited By ~ 7

Author(s):

Z. Feng ◽

R. Gollamudi ◽

G. Han ◽

Y. Tang ◽

D.W. Armstrong

Keyword(s):

Chiral Separation ◽

Nipecotic Acid

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

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y90-179 ◽

1990 ◽

Vol 68 (9) ◽

pp. 1194-1199 ◽

Cited By ~ 10

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.

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