caa a22 4500 469026200 CHVBK 20180323132730.0 cr unu---uuuuu 170328e19920601xx s 000 0 eng 10.1007/BF01962705 doi (NATIONALLICENCE)springer-10.1007/BF01962705 Löscher Wolfgang Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bunteweg 17, D-3000, Hannover, FRG aut Pharmacological, toxicological and neurochemical effects of Δ2( E )-valproate in animals [Elektronische Daten] [Wolfgang Löscher] TheE isomer of 2-ene-valproic acid (Δ2(E)-VPA) is the major active metabolite of the antiepileptic drug valproate (VPA) in various species, including humans. Experimental studies on Δ2(E)-VPA and VPA indicate that Δ2(E)-VPA may be a useful antiepileptic drug itself. Δ2(E)-VPA has the same wide spectrum of anticonvulsant activity as VPA with a somewhat higher anticonvulsant potency in rodent and dog models of different seizure types. As VPA, Δ2(E)-VPA increases presynaptic γ-aminobutyric acid (GABA) levels in the brain, presumably by an effect on GABA synthesis and/or GABA degradation. Δ2(E)-VPA is a much more potent inhibitor of the human brain GABA-degrading enzyme than VPA. In high doses. Δ2(E)-VPA is more sedative in rodents than is VPA; LD50 values are about the same. In mouse and rat models for teratogenicity, Δ2(E)-VPA does not induce teratogenic effects, whereas VPA is teratogenic in these models. Pilot rat studies on liver toxicity of VPA and VPA metabolites suggest that Δ2(E)-VPA is not hepatotoxic. In view of the rare but serious hepatotoxicity and teratogenicity of VPA in humans, Δ2(E)-VPA obviously merits interest as a valuable alternative drug in antiepileptic therapy. Royal Dutch Association for Advancement of Pharmacy, 1992 Animals, laboratory nationallicence Drug evaluation nationallicence Neuropharmacology nationallicence 2- n -Propyl-2-pentenoic acid nationallicence Scizures nationallicence Side effects nationallicence Teratogens nationallicence Toxicology nationallicence Valproic acid nationallicence Pharmaceutisch Weekblad Kluwer Academic Publishers 14/3(1992-06-01), 139-143 0031-6911 14:3<139 1992 14 11096 https://doi.org/10.1007/BF01962705 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01962705 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Löscher Wolfgang Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Bunteweg 17, D-3000, Hannover, FRG aut NATIONALLICENCE 773 0- Pharmaceutisch Weekblad Kluwer Academic Publishers 14/3(1992-06-01), 139-143 0031-6911 14:3<139 1992 14 11096 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer