High-affinity antagonists of the locust neuronal octopamine receptor

The pharmacological antagonistic properties of the invertebrate specific octopamine receptor were investigated using a conventional radio-receptor assay with [3H]octopamine as the radioligand. Among the antagonists with highest affinity of the locust (Locusta migratoria L.) neuronal octopamine receptor were tetracyclic substances like mianserin (K1 = 1.2 nM), some of its derivatives (8-hydroxymianserin; K1 = 1.68 nM), and maroxepine, which is the antagonist with the highest affinity ever reported (K1 = 1.02 nM) to this octopamine receptor class. Among the other antagonists tested only phentolamine (K1 = 19 nM) and promethazine (K1 = 31.2 nM) had high-affinity properties.