Comparative Study of the Effects Exerted by N-Valproyl-L-Phenylalanine and N-valproyl-L-tryptophan on CA1 Hippocampal Epileptiform Activity in Rat
| Autor: | Giuseppe Ferraro, Giuditta Gambino, Viviana De Caro, Pierangelo Sardo, Flavia Maria Sutera, Valerio Rizzo, Fabio Carletti, Libero Italo Giannola |
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| Přispěvatelé: | Carletti F, Rizzo V, Gambino G, De Caro V, Sutera FM, Giannola LI, Ferraro G, Sardo P. |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Phenylalanine Potassium chemistry.chemical_element Pharmacology Hippocampal formation Calcium Inhibitory postsynaptic potential Hippocampus Settore BIO/09 - Fisiologia 03 medical and health sciences antiepileptic drug 0302 clinical medicine Drug Discovery N-valproyl-L-tryptophan valproic acid medicine Animals hippocampal epilepsy Rats Wistar Valproic Acid Epilepsy Valproyl-L-Phenylalanine (VPA-Phen) Dipeptides interictal burst Rat brain Amino-acidic derivative Rats 030104 developmental biology chemistry Anticonvulsants lipids (amino acids peptides and proteins) 030217 neurology & neurosurgery medicine.drug N-valproyl-L-phenylalanine |
| Zdroj: | Current Pharmaceutical Design. 24:1849-1858 |
| ISSN: | 1381-6128 |
| Popis: | Background: The research on the improvement of epilepsy therapy is constantly growing. Valproyl-LPhenylalanine (VPA-Phen) and N-valproyl-L-tryptophan (VPA-Tryp) were synthesized to increase the antiepileptic efficacy of valproic acid. Methods: VPA-Phen and VPA-Tryp were comparatively tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0.2, 0.5, 1 mM) of VPA-Phen or VPA-Tryp. Both burst duration and interburst frequency, during and after treatment, were off-line compared with baseline values. For both parameters, either the latency or the duration of drug-induced statistically significant responses was calculated, as well as the response magnitude. Results: VPA-Phen significantly reduced both burst frequency and duration. Comparative analyses show that VPA-Phen and VPA-Tryp exert almost equivalent actions on both latency and magnitude of the observed inhibitory effects. The main observed difference between the two tested molecules concerned the duration of inhibitory effects, since VPA-Phen-dependent actions on both burst rate and duration were significantly shorter than the VPA-Tryp-induced ones. In addition, in some slices the above reported inhibitory responses were preceded by a “paradoxical” transient increase, more present at lower drug concentrations. Conclusions: Both VPA-Phen and VPA-Tryp exert significant inhibitory effects on hippocampal burst activity parameters. Although of comparable magnitude, VPA-Phen-dependent effects have a shorter duration than VPATryp- induced ones. Nevertheless, the present results confirm that the conjugation between VPA and aminoacids represents a valid tool to improve the efficacy of antiepileptic drugs and, as well as for VPA-Tryp, propose VPAPhen as a novel VPA derivative with enhanced pharmacological features. |
| Databáze: | OpenAIRE |
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