Ultra-low dose cannabinoid antagonist AM251 enhances cannabinoid anticonvulsant effects in the pentylenetetrazole-induced seizure in mice.

摘要: Several lines of evidence suggest that cannabinoid compounds are anticonvulsant since they have inhibitory effects at micromolar doses, which mediated by activated receptors coupling to Gi/o proteins. Surprisingly, both the analgesic and opioids enhanced ultra-low doses (nanomolar picomolar) opioid antagonist naltrexone as systems interact, it has been shown dose also enhances cannabinoid-induced antinociception. However, regarding seizure modulating properties classes this study investigated whether AM251 influences effects. The clonic threshold (CST) was tested in separate groups male NMRI mice following injection vehicle, selective agonist arachidonyl-2-chloroethylamide (ACEA) CB1 a combination ACEA model induced pentylenetetrazole (PTZ). Systemic administration (10 fg/kg-100 ng/kg) significantly potentiated effect 0.5 1 mg/kg. Moreover, inhibition excitatory signaling (100 pg/kg) unmasked strong for very low ng/kg-100 microg/kg), suggesting presumed component receptor can exert seizure-protective even levels activation. A similar potentiation pg/kg non-effective (0.5 mg/kg) observed generalized tonic-clonic seizure. present data antagonists may provide potent strategy modulate susceptibility, especially conjunction with cannabinoids.