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Pharmacology of the octopamine receptor from locust central nervous tissue (OAR3)

1 The present study characterized highly effective agonists from different classes of compounds for the neuronal octopamine receptor (OAR3) of the migratory locust (Locusta migratoria L.). Biogenic amines and phenyliminoimidazolidines (PIIs) were employed for the study of structure‐activity relationships. 2 The highest affinity PIIs were predominantly those with substitutions at the positions 2 and 4 of the phenolic ring (e.g. NC 7, KI = 0.3 nm, NC 8, KI = 0.81 nm). Substitutions at these positions always had positive effects on the affinity of the respective agonists. 3 Substitutions at the positions 3, 5 and 6, however, always had negative effects on the affinity. At the position one of the phenolic ring, heterocyclic substituents are preferred. 4 Some PIIs had a more than 30 times higher affinity for OARs than for α‐adrenoceptors which are the vertebrate homologues of the insect octopamine receptors. 5 The only non‐PII with subnanomolar affinity was the aminooxazoline derivative AC 6 (KI = 0.92 nm). 6 A variety of substances with known insecticidal activity such as chlordimeform, demethylchlor‐dimeform, amitraz or AC 6 had high affinity for the locust neuronal octopamine receptor.