Entrainment of circadian rhythms by S-20098, a melatonin agonist, is dose and plasma concentration dependent

The present study determined first the dose-response (0.5 to 10 mg.kg-1) to daily oral administration of S-20098, a melatonin agonist, in entraining circadian rhythms of rats free-running in constant darkness; second, the relation between entrainment and the plasma concentration of S-20098. Finally, responses to 8 mg.kg-1 of S-20098 were compared with those obtained with the same dose of melatonin and ipsapirone. Responses were classified as negative, transient, or true entrainment. The data indicated a clear dose-dependent response from 2.5 to 10 mg.kg-1 of S-20098 with an ED50 of 5.7 mg.kg-1 for true entrainment and a clear relation between entrainment and the plasma concentration of S-20098. S-20098 was as effective as melatonin to entrain free-running rhythms. Ipsapirone was ineffective in our experimental conditions.