Anticonvulsant and proconvulsant properties of viloxazine hydrochloride: pharmacological and pharmacokinetic studies in rodents and the epileptic baboon

Abstract

Viloxazine HCl is evaluated as an anticonvulsant in a wide range of rodent seizure models and in the epileptic baboon (Papio papio). In the maximal electroshock test, the oral ED50 for abolition of tonic extension was 9 mg/kg-1 after 30-min pretreatment (mouse) rising to 30 mg/kg-1 after 60 min (mouse and rat). Comparable ED50 values were also found for protection against tonic extension in the mouse induced by the administration of the chemical convulsants metrazole or 3-mercaptopropionic acid. In DBA/2 mice the ED50 for abolition of tonic extension during sound-induced seizures was 6.8 mg/kg-1 IP (30-min pretreatment). Pharmacokinetic studies in the mouse showed peak plasma levels to occur 30 min following oral doses, with a mean half-life of 58 min. The anticonvulsant plasma concentration was within 0.5 -- 1 microgram/ml-1. In the baboon, significant protection against photomyoclonic responses is observed 1 -- 2h after viloxazine (2.6 mg/kg-1 IV), during which period the plasma concentration was again 0.5-1 microgram/ml-1. After administration of approximately ten-times this latter dose level, i.e. 24 mg/kg-1 IV, a syndrome characterised by an abnormal EEG and, in some instances, seizure activity was observed.