Octopaminergic agonists

Amidines. After the initial observation that formamidines are agonists for OA receptors in the firefly (14,15 58), these compounds have been shown to mimic OA in virtually every insect system known to contain OA receptors, including the DUMETi system (59)f the glandular lobe of the corpus cardiacum (60) and the fat body ( ) of the locust, and various CNS adenylate cyclase preparations (26-28). The structure-activity relations of amidines as octopaminergic agonists have been examined in several systems including adenylate cyclase stimulation in the firefly lantern and... 

Fig. 34 General structure of 2-(arylimino)thiazolidines associated with octopaminergic agonistic activity...

At a screening concentration of 1.0 mM, none of these compounds gave noteworthy inhibition. The known phosphodiesterase inhibitors theophylline, isobutyl-3-methylxanthine (IBMX), and papaverine caused considerable inhibition at 1 mM and had IC50 values between 0.1 and 1.0 mM. It therefore seems unlikely that the excitatory effects caused by these octopaminergic agonists in invertebrates can be related to inhibition of cAMP phosphodiesterase activity. 

Carbodiimide 2 reportedly also stimulates the octopamine-sensitive adenylate cyclase of the bulb mite Rhizoglyphus echinopus [30], adults of the diamondback moth Plutella xylosteUa [31] and the lantern of the firefly Photinus pyralis, an organ known to be a rich source of octopamine-sensitive adenylate cyclase [32]. Since poisoning symptoms of diamondback moth adults treated with diafenthiuron or 2 resembled closely those of the known octopaminergic agonist... 

The only aspect of octopaminergic transmission for which a relatively large amount of structure-activity data is available relates to the properties of OA-receptors themselves. Agonists that stimulate these systems and antagonists that block them, are known and such compounds exist in several structural groups. The three major groups of agonists currently identified are phenylethylamines amidines and imidazolines. 

Through use of the virtually pure octopaminergic firefly system, we have now acquired some idea of the structure-activity requirements for activation of this octopamine-sensitive adenylate cyclase. Furthermore, by quantitating the octopamine agonist potencies of a large series of chemically-related derivatives, we are now in an excellent position to characterize octopamine receptors in other, less homogenous tissues as well as in other insect species. 

The stimulation of the octopaminergic nervous system of invertebrates is a proven strategy for the control of important pest species. This has been achieved in the past by the use of octopamine receptor agonists such as formamidine and imidazoline derivatives. However, other potential strategies to achieve this end include the inhibition of cyclic nucleotide phosphodiesterase, inhibition of the neural reuptake of octopamine, and inhibition of octopamine N-acetyltransferase. Using the American cockroach nervous system, formamidines were found to inhibit both the uptake and acetylation of octopamine, but not with a potency comparable to their effect on octopamine receptors. The tricyclic antidepressant, desipramine, and the benzylamine, xylamine, were the most active inhibitors of these octopamine removal systems. The pharmacological profiles for uptake and N-acetylation appear to be quite similar, but differ from that of the adenylate cyclase-linked octopamine receptor. 

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