Trace amines and alternative neurotransmitters in the central nervous system.

The concept of chemically mediated synaptic neurotransmission in the central nervous system (CNS) is heavily biased by our still evolving understanding of peripheral cholinergic and sympathetic neurons. The better established amine neurotransmitter candidates (especially acetylcholine, the catecholamines and serotonin) account for only a fraction of the total nerve terminals in the mammalian CNS [1]. Attempts to advance beyond traditional concepts include a growing impression that other neuro-active substances, ineluding amino acids and peptides, may account for even more of central neurotransmission than do the amines. In addition, with powerful new analytic techniques (especially radioenzymatic, and gas chromatographic-mass spectrometric methods), it has been possible to identify an increasing number of aromatic amines throughout the CNS, including phenylalkylamines, indolealkylamines and imidazoleamines [2-8]. There is increasing evidence that many such amines can be synthesized and stored in CNS nerve terminals and can be released by depolarizing stimuli 1-9-12], although their post-synaptic functional effects remain relatively obscure. That most of these substances are present in low concentrations (rig/g, or less) has sometimes led to the impression that their occurrence may be incidental to the synthesis of other "more important" amines, such as the catecholamines or serotonin (5-I-IT), for example, by the action of relatively non-selective aromatic amino acid decarboxylases on their precursors, or by the interconversion of amines by recently appre.ciated hydroxylase or dehydroxylase (redox) pathways, presumably present in neuronal tissue 1.3, 7]. Low tissue concentrations of amines in some cases may reflect varying degrees of efficiency of their protection, notably by reserpine-sensitive storage in presynaptic vesicles 1~4, 9, 13], and hence, of vulnerability to monoamine oxidase (MAO). In the case of at least one of these substances, octopamine, it is now apparent that its turnover in most neuronal tissues is very rapid, and based on the production of deaminated metabolites, the daily synthesis of octopamine in the whole body closely approaches that of the catecholamines [14]. If turnover and production rates reflect