Octopamine structure

Trace amines are a family of endogenous monoamine compounds including (3-phenylethylamine (PEA), p-tyramine (TYR), tryptamine (TRP) and octopamine (OCT). The trace amines share close structural similarity with the well known classical monoamine neurotransmitters such as dopamine (DA), norepinephrine (NE) and serotonin (5-HT). As their name suggests, trace amines occur in comparably much lower abundance than monoamine neurotransmitters. For historical reasons, other endogenous amine compounds which might share some structural similarities with PEA, TYR, TRP or OCT are not referred to as trace amines. 

False neurotransmitters are amines which are similar enough in structure to normal amine neurotransmitters that they bind to receptors but are much less active or totally inactive (i.e. they are antagonists). One such false neurotransmitter is octopamine, which is formed from tyrosine by decarboxylation followed by side-chain hydroxylation. 

The noradrenaline normally contained in the storage granules can be partly or completely replaced by structurally related sympathomimetic amines, either by injection of the amine itself, or of suitable precursors such as a-methyl-DOPA or a-methyl-w-tyrosine. These amines can be depleted from the heart by guanethidine in the same way as the noradrenaline which they had replaced. a-Methylnoradrenaline [337] and metaraminol [338] are depleted less readily than noradrenaline from rabbit or rat hearts, whereas dopamine, octopamine and w-octopamine are depleted more readily than noradrenaline [339]. The more rapid depletion of these last three compounds was attributed to weaker binding in the storage granules [339], but could equally well be due to their greater susceptibility to destruction by monoamine oxidase, since both a-methyl-noradrenaline and metaraminol are resistant to attack by monoamine oxidase. 

Figure 1. Structures of octopamine, norepinephrine, the pesticide/pestistat chlordimeform (CDM), and related compounds.

Figure 7.26 Hydrolysis of amitraz showing its hydrolysis product resembling the structure of octopamine.

Octopamine is structurally very similar to norepinephrine being different only in lacking the 3-hydroxyl group on the aromatic ring (Figure 1). It may therefore be considered the monophenolic analogue of norepinephrine. In the vertebrate nervous system octopamine is synthesized by a decarboxylation of tyrosine to tyramine, and then by a subsequent 8-hydroxylation of tyramine (15). Whilst the enzymes have not been purified and characterized in insects a similar pathway appears to occur, since radiolabelled tyrosine and tyramine may be metabolized to octopamine by insect nervous tissue (3,16-17). 

Octopamine ( -hydroxyphenylethanolamine) was first discovered in the posterior salivary gland of the octopus over 30 years ago by Erspamer and Boretti (4). Although similar to norepinephrine in structure, octopamine was soon found to have very little activity as a sympathomimetic when injected into mammals (5). In addition, compared with norepinephrine, octopamine was found to be present in very low concentrations in vertebrate tissues (6) Because of these facts, relatively little attention was paid to octopamine until the early 1970 s, when Molinoff and Axelrod (7) developed a sensitive radioenzymatic assay for the compound and reported that octopamine was present in much higher concentrations in invertebrates, particularly in invertebrate nerve tissue ... 

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 studies discussed herein show that formamidines without the conventional lethal moiety can elicit dispersal behavior and can interfere with reproduction in twospotted spider mites. Walk-off dispersal elicited by formamidines was correlated with formamidine-induced mortality. Since these structure-activity relationships of formamidines are similar to those for pertubation of octopa-minergic transmission in insects, a similar mechanism could be involved in these actions in mites. Since structure-activity relationships for formamidine effects on spin-down and reproduction were not correlated with those for lethality, other mechanisms, which may or may not involve octopamine or other biogenic amines, are probably associated with these actions. 

Synephrine [l-p-hydroxy-a-(methylaminomethyl)benzyl alcohol] (51) and its lower homolog, octopamine (52) have been isolated from the leaves of lemon trees (Citrus spp.) though previously they had only been found in animals (52). Further examination of the grapefruit led to the isolation of a base, feruloylputreseine (53), which is the structure assigned to subaphylline first isolated from the unrelated SaUola subaphylla C. A. Mey. (54). 

---