Title : Arachidonyl-2’-chloroethylamide enhances the anticonvulsant potency of levetiracetam in psychomotor seizure test in mice
Abstract:
The aim of this study was to evaluate the influence of arachidonyl-2’-chloroethylamide (ACEA – a potent and selective cannabinoid CB1 receptor agonist) on the anticonvulsant properties of six selected antiepileptic drugs (i.e., clobazam, lacosamide, levetiracetam, phenobarbital, tiagabine and valproate) in the mouse psychomotor (limbic) seizure model.
Psychomotor (limbic) seizures were evoked in adult male albino Swiss mice by a current (6 Hz, 0.2 ms rectangular pulse width, 32 mA, 3 s duration) delivered via ocular electrodes.Potential concurrent adverse-effect profiles of interaction between ACEA and six selected antiepileptic drugs were evaluated in the chimney test (motor performance), passive avoidance task (long-term memory) and grip-strength test (skeletal muscular strength) in mice. Total brain antiepileptic drug concentrations were measured with HPLC to exclude any pharmacokinetic interaction between drugs.
Results indicate that the selective cannabinoid CB1 receptor agonist ACEA significantly potentiated the anticonvulsant effects of levetiracetam against psychomotor (limbic) seizures in mice. In contrast, ACEA had no significant impact on the anticonvulsant effects of clobazam, lacosamide, phenobarbital, tiagabine and valproate in this seizure model. No potential adverse effects associated with the combined treatment of ACEA with six antiepileptic drugs were observed in these behavioral tests in mice. Pharmacokinetic experiments revealed that ACEA did not significantly affect total brain concentrations of levetiracetam in mice and thus, the observed interaction was pharmacodynamic in nature.
In conclusions, significant potentiation of the anticonvulsant effects of levetiracetam by the selective cannabinoid CB1 receptor agonist ACEA in the mouse psychomotor seizure model might be translated to clinical conditions. It seems that activation of cannabinoid system in the brain results in suppression of psychomotor seizures, however, this fact needs confirmation in further clinical studies.
Audience take away:
- This study is another example that cannabinoids with some drugs can protect agains sizures. Interaction between levetriacetam and ACEA can be translated to clinical conditions in the future
- ACEA is another substance that can be treated in the future, as a substance that protects agains sizures.
- The study can be used as an exaple to teach about effects of cannabinoid receptors.
- ACEA can be a solution for patients treated by levetriacetam, as a substance that increase antiepileptic effect.
