PHARMACOLOGY OF THE OCTOPAMINE RECEPTOR FROM LOCUST CENTRAL NERVOUS-TISSUE (OAR3)

1 The present study characterized highly effective agonists from diffe rent classes of compounds for the neuronal octopamine receptor (OAR(3) ) of the migratory locust (Locusta migratoria L.). Biogenic amines and phenyliminoimidazolidines (PIIs) were employed for the study of struc ture-activity relationships. 2 The highest affinity PIIs were predomin antly those with substitutions at the positions 2 and 4 of the phenoli c ring (e.g. NC 7, K-1 = 0.3 nM, NC 8, K-1 = 0.81 nM). Substitutions a t these positions always had positive effects on the affinity of the r espective agonists. 3 Substitutions at the positions 3, 5 and 6, howev er, always had negative effects on the affinity, At the position one o f the phenolic ring, heterocyclic substituents are preferred. 4 Some P IIs had a more than 30 times higher affinity for OARs than for alpha-a drenoceptors which are the vertebrate homologues of the insect octopam ine receptors. 5 The only non-PII with subnanomolar affinity was the a minooxazoline derivative AC 6 (K-1 = 0.92 nM). 6 A variety of substanc es with known insecticidal activity such as chlordimeform, demethylchl ordimeform, amitraz or AC 6 had high affinity for the locust neuronal octopamine receptor.