Anticonvulsant effects of N-arachidonoyl-serotonin, a dual fatty acid amide hydrolase enzyme and transient receptor potential vanilloid type-1 (TRPV1) channel blocker, on experimental seizures: the roles of cannabinoid CB1 receptors and TRPV1 channels
| Autor: | Márcio Flávio Dutra Moraes, Antônio Carlos Pinheiro de Oliveira, Daniel de Castro Medeiros, Fabrício A. Moreira, Luciano R. Vilela |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
AM251
Male Serotonin Cannabinoid receptor medicine.medical_treatment TRPV1 TRPV Cation Channels Arachidonic Acids Pharmacology Toxicology Amidohydrolases chemistry.chemical_compound Mice Piperidines Receptor Cannabinoid CB1 Fatty acid amide hydrolase Seizures medicine Animals Anilides musculoskeletal neural and ocular physiology General Medicine Anandamide Anticonvulsant nervous system chemistry Arachidonoyl serotonin Cinnamates Pentylenetetrazole Pyrazoles lipids (amino acids peptides and proteins) Anticonvulsants Cannabinoid psychological phenomena and processes medicine.drug |
| Zdroj: | Basicclinical pharmacologytoxicology. 115(4) |
| ISSN: | 1742-7843 |
| Popis: | Selective blockade of anandamide hydrolysis, through the inhibition of the FAAH enzyme, has anticonvulsant effects, which are mediated by CB1 receptors. Anandamide, however, also activates TRPV1 channels, generally with an opposite outcome on neuronal modulation. Thus, we suggested that the dual FAAH and TRPV1 blockade with N-arachidonoyl-serotonin (AA-5-HT) would be efficacious in inhibiting pentylenetetrazole (PTZ)-induced seizures in mice. We also investigated the contribution of CB1 activation and TRPV1 blockade to the overt effect of AA-5-HT. In the first experiment, injection of AA-5-HT (0.3-3.0 mg/kg) delayed the onset and reduced the duration of PTZ (60 mg)-induced seizures in mice. These effects were reversed by pre-treatment with the CB1 antagonist, AM251 (1.0-3.0 mg/kg). Finally, we observed that administration of the selective TRPV1 antagonist, SB366791 (0.1-1 mg/kg), did not entirely mimic AA-5-HT effects. In conclusion, AA-5-HT alleviates seizures in mice, an effect inhibited by CB1 antagonism, but not completely mimicked by TRPV1 blockage, indicating that the overall effect of AA-5-HT seems to depend mainly on CB1 receptors. This may represent a new strategy for the development of drugs against seizures, epilepsies and related syndromes. |
| Databáze: | OpenAIRE |
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