lacosamide and Epilepsy--Complex-Partial

Topics: Aged; Anticonvulsants; Atrioventricular Block; Bacterial Infections; Clonazepam; Epilepsy, Complex Partial; Female; Humans; Lacosamide; Levetiracetam; Propofol; Valproic Acid

Accumulating evidence indicates that cannabinoid CB1 receptor ligands play a pivotal role in seizures, not only in preclinical studies on animals, but also in clinical settings. This study was aimed at characterizing the influence of arachidonyl-2'-chloroethylamide (ACEA-a selective cannabinoid CB1 receptor agonist) co-administered with phenylmethylsulfonyl fluoride (PMSF) on the anticonvulsant potency of various antiepileptic drugs (clobazam, lacosamide, levetiracetam, phenobarbital, tiagabine and valproate) in the 6-Hz corneal stimulation model. Psychomotor seizures in male albino Swiss mice were evoked by a current (32 mA, 6 Hz, 3 s stimulus duration) delivered via corneal electrodes. Potential adverse effects produced by the antiepileptic drugs in combination with ACEA+PMSF were assessed using the chimney test (motor performance), passive avoidance task (remembering and acquisition of learning), and grip-strength test (muscular strength). Brain concentrations of antiepileptic drugs were measured by HPLC to exclude any pharmacokinetic contribution to the observed effect. ACEA (5 mg/kg, i.p.) + PMSF (30 mg/kg, i.p.) significantly potentiated the anticonvulsant potency of levetiracetam (P<0.05), but not that of clobazam, lacosamide, phenobarbital, tiagabine or valproate in the 6-Hz corneal stimulation model. Moreover, ACEA+PMSF did not significantly affect total brain concentrations of levetiracetam in mice. No behavioral side effects were observed in animals receiving combinations of the studied antiepileptic drugs with ACEA+PMSF. In conclusion, the combined administration of ACEA+PMSF with levetiracetam is associated with beneficial anticonvulsant pharmacodynamic interaction in the 6-Hz corneal stimulation model. The selective activation of cannabinoid CB1 receptor-mediated neurotransmission in the brain may enhance levetiracetam-related suppression of seizures in epilepsy patients, contributing to the efficacious treatment of epilepsy in future.

Topics: Acetamides; Animals; Anticonvulsants; Arachidonic Acids; Avoidance Learning; Benzodiazepines; Clobazam; Cornea; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Electroshock; Epilepsy, Complex Partial; Lacosamide; Levetiracetam; Male; Mice; Muscle Strength; Nipecotic Acids; Phenobarbital; Phenylmethylsulfonyl Fluoride; Piracetam; Psychomotor Performance; Receptor, Cannabinoid, CB1; Tiagabine; Valproic Acid

Topics: Acetamides; Adult; Anticonvulsants; Epilepsy, Complex Partial; Hallucinations; Humans; Lacosamide; Male