HORMONAL STATUS OF RH-5849 AND RH-5992 SYNTHETIC ECDYSONE AGONISTS (ECDYSOIDS) EXAMINED ON SEVERAL STANDARD BIOASSAYS FOR ECDYSTEROIDS

Effects of the synthetic ecdysone agonists RH-5849 and RH-5992 have be en compared with the action of 20-hydroxyecdysone in several standard bioassays that are currently used for determination of the moulting ho rmone activity. In the assay on ligated larvae of Galleria, these synt hetic hormone mimics, ecdysoids according to the endocrinological term inology, stimulated the extra-larval moult cycles with all development al consequences similar to the action of 20-hydroxyecdysone. The ED-50 dosages were 1.3 mu g for 20-hydroxyecdysone, 1.75 mu g for RH-5849 a nd 0.9 mu g/specimen for RH-5992. In the assays on diapausing pupae of Manduca and Pieris, RH-5849 also duplicated the developmental stimula tion of 20-hydroxyecdysone at lower concentrations (in Manduca, ED-50 1.2 mu g/spec. for RH-5849, 1.9 mu g for 20-hydroxyecdysone; in Pieris , ED-50 0.013 mu g for RH-5849, 0.1 mu g for 20-hydroxyecdysone). When compared with 20-hydroxyecdysone, the ecdysoids caused pathophysiolog ical symptoms of hyper-ecdysonismm or neurotoxic action at much lower concentrations, corresponding to the bottom of the dose-response curve s. Both the ecdysoids were completely ineffective in the standard assa ys on ligated larvae of Sarcophaga and Calliphora and they were equall y inactive in all methods of topical application that have been used. In special assays on larvae of Galleria, the ecdysoid RH-5849 exhibite d definite synergistic action with 20-hydroxyecdysone, there was no an tagonism. The results confirm previous conclusions that these syntheti c ecdysoids act directly at the peripheral tissue targets. The reasons in favour and against a hypothesis that they would act by inducing en dogenous ecdysteroid synthesis in the target cells has been discussed.