Chronopharmacological studies of neuroleptics

Studies were carried out to clarify the mechanism of appearance and the laws controlling the appearance of such phenomena as circadian fluctuation in the effects of neuroleptics. A detailed review was initially made of previous studies on drugs closely related to neuroleptics; then data obtained by the authors was analyzed. Significant circadian fluctuation was found in the effect of chlorpromazine, haloperidol, and tetrabenazine, varying with the time of administration, with the kind of drug, and even with the dose of the same drug. There was also circadian fluctuation in lethality rate, which was seen to be a phenomenon controlled by a law different from that controlling circadian fluctuation in the effect of a drug. Circadian fluctuation in the effect of a drug was regulated externally by clock time, setting the light-dark rhythm of the raising environment. Different times of administration of a drug did not affect chronological changes in the blood level or intracerebral concentration of a drug after administration. From these results, it was assumed that this phenomenon might be induced by the circadian rhythm of drug sensitivity of a brain where the drug acts.