Drawing Inferences about the Therapeutic Efficacy of Drugs in Patients from their CNS Effect in Normals: Comparative Quantitative Pharmaco-EEG and Clinical Investigations

摘要: ABSTRACT In two subsequent studies the question was explored to which extent short-term drug effects in EEG of normal subjects are predictive clinical and patients. Early Phase I trials volunteers suggested that D-12524 (lopirazepam – a new pyridodiazepine) is CNS-effective substance differs significantly from placebo produces pharmaco-EEG profile typical for “anxiolytic” drugs. Indeed, study alcoholic patients with an anxiety syndrome confirmed this prediction. During three-week treatment period marked significant improvement noted symptomatology as evaluated by means global score, Hamilton, Zung Erlanger somatic symptoms side effect rating scale psychometric test methods. Comparing central certain dosage (at same time after oral administration) different populations, it found lopirazepam produced type changes, although some quantitative differences especially slow waves (sedative effect) were obvious. But then there also baseline between brain activity alcoholics normals. Single dose highly correlated alterations three weeks chronic administration drug. Moreover, drug-induced changes during therapy linked or deterioration. Finally, relationships single-dose therapeutic outcome investigated.