Principles of Chronopharmacology and the Sleep-Wake Rhythm

Abstract

The first studies showing that a given effect of a drug was dependent on time of dosing were carried out on narcotics. Virey (1814) reported that following the recommendations of Thomas Sydenham he prescribed the use of opium (in the form of laudanum) as a narcotic during the late evening hours rather than during the morning or another time of day. Thus, even in 1814 Virey considered the potential existence of biological clocks and emphasized that a change in the effectiveness of drugs as a function of the dosing time was related to changes in the subject’s susceptibility. One hundred and fifty years later it was confirmed that some pharmacological agents able to induce sleep and related processes operate more efficiently when they are administered during evening or night hours in diurnally active subjects. This was the case for: halothane (Fukami et al. 1970), best efficiency between midnight and 6 a.m. (0600h); ethanol (Reinberg et al. 1975), maximum self-rated inebriety and poorer psychological performance with ethanol (0.67 g/kg body weight) at 11 p.m. (2300 h) as compared with other dosing times (7 a.m., 11 a.m., 7 p.m.); and 3–alkyl pyrazolyl piperazine (Simpson et al. 1973), better subjective “quality” of sleep and less broken sleep than control (placebo) when administered in the morning.