Chronopharmacology and Chronotoxicology of CNS Drugs: Interrelationships with Neuromodulators

It has been demonstrated that the effect of a drug, chemical, or poison is diurnal phase dependent. The circadian variation in drug response could be attributed to the diurnal fluctuations of several factors, including absorption, distribution, metabolism, and excretion. Another important factor in determining the response to CNS drugs is the circadian rhythm of brain sensitivity to drugs. The diurnal variability in the concentration of brain neuromodulators could in part explain the circadian rhythm of brain sensitivity. The present paper focuses on the interrelationships between the levels of neuromodulators and the chronopharmacology and chronotoxicology of CNS drugs. Evidence is presented to show that the circadian rhythm of specific brain neuromodulators plays an important role in the pharmacologic or toxicologic action of amphetamine, barbiturates, morphine, and ethanol.