Drug Res (Stuttg) 2021; 71(02): 94-103
DOI: 10.1055/a-1290-0119
Original Article

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

1   MM College of Pharmacy, MM (Deemed to be University), Mullana, Ambala, Haryana
,
1   MM College of Pharmacy, MM (Deemed to be University), Mullana, Ambala, Haryana
,
Dinesh Kumar Mehta
1   MM College of Pharmacy, MM (Deemed to be University), Mullana, Ambala, Haryana
,
Rina Das
1   MM College of Pharmacy, MM (Deemed to be University), Mullana, Ambala, Haryana
› Author Affiliations
Funding The authors want to thank to MM College of Pharmacy, MM (Deemed to be University), for all the financial supports for the work.

Abstract

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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Graphical Abstract



Publication History

Received: 14 August 2020

Accepted: 12 October 2020

Article published online:
25 November 2020

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