Stereoselective pharmacokinetic and pharmacodynamic analysis of a CNS-active sulphamoylphenyl carbamate derivative.
Animals
Anticonvulsants
/ chemical synthesis
Carbamates
/ chemical synthesis
Carbonic Anhydrase Inhibitors
/ chemical synthesis
Carbonic Anhydrases
/ metabolism
Central Nervous System
/ drug effects
Central Nervous System Agents
/ chemical synthesis
Dose-Response Relationship, Drug
Male
Molecular Structure
Rats
Rats, Sprague-Dawley
Stereoisomerism
Structure-Activity Relationship
4-aminobenzenesulphonamides
CNS-active carbamates
New antiepileptic drugs
carbonic anhydrase inhibition
pharmacokinetics
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
entrez:
25
5
2019
pubmed:
28
5
2019
medline:
18
6
2019
Statut:
ppublish
Résumé
3-Methylpentyl(4-sulphamoylphenyl)carbamate (MSPC) came as the most potent compound out of a new series of carbamates composed of phenyl-ethanol or branched aliphatic alcohols, and 4-benzenesulphonamide-carbamic acid. In this study, the anticonvulsant activity and pharmacokinetics (PKs) of MSPC-two individual enantiomers were comparatively analysed in rats as well as their carbonic anhydrase (CA) inhibition. The anticonvulsant activity of MSPC enantiomers was evaluated at the rat-maximal electroshock (MES) test, and their CA inhibition evaluated. (R)-MSPC had a 29% higher clearance and consequently, a lower plasma exposure area under the curve (AUC) than (S)-MSPC and racemic-MSPC. Nevertheless, (R)-MSPC had a better brain permeability than its (S)-enantiomer with brain-to-plasma-(AUC)-ratio (BPR) of 2.07 ((R)-enantiomer), 1.85 (racemate), and 0.79 ((S)-enantiomer). As a whole body (
Identifiants
pubmed: 31124389
doi: 10.1080/14756366.2019.1612887
pmc: PMC6534253
doi:
Substances chimiques
3-methylpentyl(4-sulphamoylphenyl)carbamate
0
Anticonvulsants
0
Carbamates
0
Carbonic Anhydrase Inhibitors
0
Central Nervous System Agents
0
Carbonic Anhydrases
EC 4.2.1.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1078-1082Références
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