HRONIC FATIGUE SYNDROME (CFS) is a complex disorder characterized by long-term disability. The rate of spontaneous recovery in CFS is low 1 and no consistently effective treatment is available. Hypoactivity of the hypothalamicpituitary-adrenal axis has been demonstrated in some patients with CFS and fibromyalgia. 2-7 Some evidence suggests that CFS patients may have enhanced sensitivity of the peripheral cholinergic vascular system and an exaggerated pyridostigmine-stimulated growth hormone release response. 8 Acetylcholine is implicated in vagal tone, baroreceptor reflexes, and in transmission at the nicotinic sympathetic ganglia and at the neuromuscular junctions. Patients with CFS are often intolerant of the anticholinergic adverse effects of tricyclic antidepressants and these symptoms are similar to the symptoms of CFS. The frequent complaint of cognitive impairment in CFS also is consistent with the cholinergic hypothesis of cognition. A functional deficiency of cholinergic neurotransmission offers one possible explanation for the findings of a hypoactive hypothalamic-pituitary-adrenal axis; under conditions of stress, acetylcholine facilitates the release of corticotrophin-releasing hormone. Cholinergic stimulation also releases

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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.