Anticonvulsant and proconvulsant properties of viloxazine hydrochloride: pharmacological and pharmacokinetic studies in rodents and the epileptic baboon. 1982

B S Meldrum, and G M Anlezark, and H K Adam, and D T Greenwood

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008808 Mice, Inbred CBA An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH. Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D009025 Morpholines Tetrahydro-1,4-Oxazines,Tetrahydro 1,4 Oxazines
D010215 Papio A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of five named species: PAPIO URSINUS (chacma baboon), PAPIO CYNOCEPHALUS (yellow baboon), PAPIO PAPIO (western baboon), PAPIO ANUBIS (or olive baboon), and PAPIO HAMADRYAS (hamadryas baboon). Members of the Papio genus inhabit open woodland, savannahs, grassland, and rocky hill country. Some authors consider MANDRILLUS a subgenus of Papio. Baboons,Baboons, Savanna,Savanna Baboons,Baboon,Baboon, Savanna,Papios,Savanna Baboon
D003292 Convulsants Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. Convulsant,Convulsant Effect,Convulsant Effects,Effect, Convulsant,Effects, Convulsant
D004597 Electroshock Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. Electroconvulsive Shock,Electroconvulsive Shocks,Electroshocks,Shock, Electroconvulsive,Shocks, Electroconvulsive
D004827 Epilepsy A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313) Aura,Awakening Epilepsy,Seizure Disorder,Epilepsy, Cryptogenic,Auras,Cryptogenic Epilepsies,Cryptogenic Epilepsy,Epilepsies,Epilepsies, Cryptogenic,Epilepsy, Awakening,Seizure Disorders
D005260 Female Females

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