Chronopharmacology of strophanthin and inderal: an experimental study

Chronopharmacological investigations were performed in 54 guinea pigs and 126 white mice to explore their tolerance to arrhythmogenic and lethal doses of strophanthin, and changes in sensitivity to threshold antiarrhythmic dose of inderal during 24 hours. The investigations were carried out at a 4-hour interval, i.e., six times in 24 hours. The data obtained were processed using the approximation method to determine sinusoid fluctuations with an initially given period (cosinor analysis) and with an unknown period (non-linear least-square method in combination with the method of gradual approximation) on an EC 1045 computer and a DZ 28 microcomputer. It was found that strophanthin toxicity in guinea pigs and white mice reaches a maximum in the late evening, night and early morning hours. The acrophases of circadian rhythms of chronotolerance to the threshold arrhythmogenic dose of strophanthin, and those of chronosensibility to inderal are virtually identical.