Design, Synthesis and Enhanced BBB Penetration Studies of L-serine-Tethered Nipecotic Acid-Prodrug.
Animals
Anticonvulsants
/ chemical synthesis
Biological Transport
/ drug effects
Blood-Brain Barrier
/ metabolism
Esters
/ chemical synthesis
Hydrophobic and Hydrophilic Interactions
Male
Mice
Nipecotic Acids
/ chemical synthesis
Pentylenetetrazole
/ chemical synthesis
Prodrugs
/ chemical synthesis
Seizures
/ drug therapy
Serine
/ chemical synthesis
Journal
Drug research
ISSN: 2194-9387
Titre abrégé: Drug Res (Stuttg)
Pays: Germany
ID NLM: 101602406
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
pubmed:
27
11
2020
medline:
8
10
2021
entrez:
26
11
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Anticonvulsants
0
Esters
0
Nipecotic Acids
0
Prodrugs
0
nipecotic acid
1U1QTN40SY
Serine
452VLY9402
Pentylenetetrazole
WM5Z385K7T
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
94-103Informations de copyright
Thieme. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest, financial or otherwise