In:
Basic & Clinical Pharmacology & Toxicology, Wiley, Vol. 115, No. 4 ( 2014-10), p. 330-334
Kurzfassung:
Selective blockade of anandamide hydrolysis, through the inhibition of the FAAH enzyme, has anticonvulsant effects, which are mediated by CB 1 receptors. Anandamide, however, also activates TRPV 1 channels, generally with an opposite outcome on neuronal modulation. Thus, we suggested that the dual FAAH and TRPV 1 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 CB 1 activation and TRPV 1 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 CB 1 antagonist, AM 251 (1.0–3.0 mg/kg). Finally, we observed that administration of the selective TRPV 1 antagonist, SB 366791 (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 CB 1 antagonism, but not completely mimicked by TRPV 1 blockage, indicating that the overall effect of AA ‐5‐ HT seems to depend mainly on CB 1 receptors. This may represent a new strategy for the development of drugs against seizures, epilepsies and related syndromes.
Materialart:
Online-Ressource
ISSN:
1742-7835
,
1742-7843
DOI:
10.1111/bcpt.2014.115.issue-4
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2014
ZDB Id:
2151592-X
SSG:
15,3
Permalink