title: Proof of safety of drugs: focus on vigilance.
abstract: It is well accepted that all new compounds, before administration to patients, should undergo safety evaluations in healthy subjects, including central nervous system (CNS) toxicity and as such the assessment of vigilance effects a relevant hallmark. The original concept of vigilance as a phenomenon observed only under conditions of monotony and signal regularity is increasingly falling into disfavor, embracing at present a much broader spectrum of behavior. Currently, vigilance may be regarded as a "readiness to adopt the appropriate behavior in a given situation, which thus finds outward expression through the quality and quantity of the behavior occurring in response to a given (internal or external) stimulus situation". The assumption that vigilance is a multifactorial phenomenon and not merely EEG data should be taken into account in order to study it accurately. Specifically, in drug research, apart from subjective reports and psychomotor performance tests, neurophysiological evaluations are regularly used such as Multiple Sleep Latency Test, Vigilance Epoch Classification or Parameters within a continuous scale. Although with limitations, temporal patterns of changes in activity of different frequency bands, indexes as the alpha slow-wave or the alpha anteriorization, computed from the EEG quantification, yielded different definitions of the intermediate states of the transition from wakefulness to sleep through the so-called subvigil stages. Spatial patterns are less documented. The recently proposed mathematical models to explain and predict variations in alertness are presented. Examples of the effects of different classes of drugs with the methods reported and its theoretical and practical relevance to vigilance research are introduced.
authors.affiliation: Centre d'Investigació de Medicaments, Institut de Recerca, Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Barbanoj
authors.forename: J L
authors.initials: JL
authors.lastname: Lorenzo
authors.forename: S
authors.initials: S
authors.lastname: Clos
authors.forename: C
authors.initials: C
authors.lastname: García-Gea
authors.forename: F
authors.initials: F
authors.lastname: Jané
mesh_terms: D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D004569:Electroencephalography / Q000187:drug effects* / Q000706:statistics & numerical data; D006801:Humans; D008954:Models, Biological