In vitro effects of antiepileptic drugs on acetylcholinesterase and ectonucleotidase activities in zebrafish (Danio rerio) brain.
Carbamazepine (CBZ), phenytoin (PHT), and gabapentine (GBP) are classical antiepileptic drugs (AEDs) that act through a variety of mechanisms. We have tested the in vitro effects of CBZ, PHT, and GBP at different concentrations on ectonucleotidase and acetylcholinesterase activities in zebrafish brain. CBZ inhibited ATP hydrolysis at 1000 microM (32%) whereas acetylcholine hydrolysis decreased at 500 microM (25.2%) and 1000 microM (38.7%). PHT increased AMP hydrolysis both at 500 microM (65%) and 1000 microM (64.8%). GBP did not promote any significant changes on ectonucleotidase and acetylcholinesterase activities. These results have shown that CBZ can reduce NTPDase (nucleoside triphosphate diphosphohydrolase) and PHT enhance ecto 5'-nucleotidase activities. Therefore, it is possible to suggest that the AEDs induced-effects on ectonucleotidases are related to enzyme anchorage form. Our findings have also shown that high CBZ concentrations inhibit acetylcholinesterase activity, which can induce an increase of acetylcholine levels. Taken together, these results showed a complex interaction among AEDs, purinergic, and cholinergic systems, providing a better understanding of the AEDs pharmacodynamics.
Siebel
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AM
Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul. Avenida Ipiranga, 6681, 90619-900 Porto Alegre, RS, Brazil.
Rico
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Capiotti
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KM
Piato
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AL
Cusinato
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CT
Franco
T M A
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Bogo
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Bonan
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D015720:5'-Nucleotidase / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000588:Amines / Q000633:toxicity; D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002220:Carbamazepine / Q000633:toxicity; D003509:Cyclohexanecarboxylic Acids / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D000077206:Gabapentin; D010672:Phenytoin / Q000633:toxicity; D015027:Zebrafish / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000633:toxicity
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D000077206:Gabapentin; D000110:Acetylcholinesterase; D015720:5'-Nucleotidase