caa a22 4500 477128297 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19970201xx s 000 0 eng 10.1023/A:1012009012850 doi (NATIONALLICENCE)springer-10.1023/A:1012009012850 Pharmacokinetics and Antiepileptic Activity of Valproyl Hydroxamic Acid Derivatives [Elektronische Daten] [Micha Levi, Boris Yagen, Meir Bialer] Purpose. To explore the utilization of seven novel hydroxamic acid derivatives of valproic acid (VPA) as new antiepileptics. Methods. The study was carried out by investigating the pharmacokinetics of two active compounds in dogs and pharmacodynamics (anti-convulsant activity and neurotoxicity) of valproyl hydroxamic acid and six of its derivatives. Results. Three valproyl hydroxamic acid derivatives: valproyl hydroxamic acid—VPA-HA, N-(l-hydroxyethyl)-valpromide—HEV and N-methoxy valpromide, showed better anticonvulsant activity than VPA at the maximal electroshock (MES) test. The remaining four compounds, O-valproyl-VPA-HA, N-valproyl-O-valproyl-VPA-HA, N-(l-methoxyethyl) valpromide and N-( 1,2-dihydroxylpropyl)-valpromide were found to be inactive. Therefore, only the pharmacokinetics of the active compounds VPA-HA and HEV was studied. Conclusions. In contrast to valpromide (VPD) which is biotransformed to VPA, VPA-HA and HEV were found to be stable in vivo to the biotransformation of the amide to its corresponding acid. VPA-HA and HEV showed improved anticonvulsant activity over VPA because of their greater intrinsic activity and not due to better pharmacokinetic characteristics. This paper discusses the structural requirements for active anticonvulsant valproyl hydroxamic acid derivatives. Plenum Publishing Corporation, 1997 valproic acid nationallicence valproyl hydroxamic acid derivatives nationallicence pharmacokinetics nationallicence antiepileptic activity nationallicence structural requirements nationallicence Levi Micha aut Yagen Boris aut Bialer Meir aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 213-217 0724-8741 14:2<213 1997 14 11095 https://doi.org/10.1023/A:1012009012850 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012009012850 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Levi Micha aut NATIONALLICENCE 700 1- Yagen Boris aut NATIONALLICENCE 700 1- Bialer Meir aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/2(1997-02-01), 213-217 0724-8741 14:2<213 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer