Targeting γ-Aminobutyric Acid (GABA) Carriers to the Brain: Potential Relevance as Antiepileptic Pro-Drugs

Title: Targeting γ-Aminobutyric Acid (GABA) Carriers to the Brain: Potential Relevance as Antiepileptic Pro-Drugs

Volume: 6 Issue: 3

Author(s): Mohammad H. Semreen, Abdel-Nasser El-Shorbagi, Taleb H. Al-Tel and Izzeddin M.M. Alsalahat

Affiliation:

Keywords: GABA, antiepileptic, pro-drugs, blood brain barrier, tetrahydro-2H-1,3, 5-thiadiazine-2-thione

Abstract: The search for antiepileptic compounds with more selective activity continues to be an area of intensive investigation in medicinal chemistry. 3,5-Disubstituted tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) derivatives, 3a-g, potential prodrugs incorporating the neurotransmitter GABA were synthesized and studied for crossing the blood-brain barrier (BBB). Compounds were prepared from primary amines and carbon disulfide to give dithiocarbamates 2a-g which upon reaction in situ with formaldehyde provided the intermediates Ia-g. Addition of Ia-g onto GABA furnished the title compounds 3a-g. The structures were verified by spectral data and the amounts of the compounds in the brain were investigated by using HPLC. The concentration profiles of the tested compounds in mice brain were determined and the in vivo anticonvulsant activity was measured.

Cite this article as:

Semreen H. Mohammad, El-Shorbagi Abdel-Nasser, Al-Tel H. Taleb and Alsalahat M.M. Izzeddin, Targeting γ-Aminobutyric Acid (GABA) Carriers to the Brain: Potential Relevance as Antiepileptic Pro-Drugs, Medicinal Chemistry 2010; 6 (3) . https://dx.doi.org/10.2174/1573406411006030144