title: Targeting γ-aminobutyric acid (GABA) carriers to the brain: potential relevance as antiepileptic pro-drugs.
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.
authors.affiliation: College of Pharmacy, University of Sharjah, Sharjah-27272, UAE. msemreen@sharjah.ac.ae
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Semreen
authors.forename: Abdel-Nasser
authors.initials: AN
authors.lastname: El-Shorbagi
authors.forename: Taleb H
authors.initials: TH
authors.lastname: Al-Tel
authors.forename: Izzeddin M M
authors.initials: IM
authors.lastname: Alsalahat
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy*; D005260:Female; D018755:GABA Agonists / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D023421:Models, Animal; D010433:Pentylenetetrazole / Q000633:toxicity; D011355:Prodrugs / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013843:Thiazines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D005680:gamma-Aminobutyric Acid
chemical_list: D018755:GABA Agonists; D011355:Prodrugs; D013843:Thiazines; D013871:Thiones; D005680:gamma-Aminobutyric Acid; D010433:Pentylenetetrazole