Elusive amines and primary headaches: historical background and prospectives.

Although the role of trace amines such as tyramine, octopamine and synephrine in the pathogenesis of migraine has been debated for decades, this issue remains still unresolved. In spite of a relevant body of work, the inability to demonstrate specific receptors for these compounds and the lack of sensitive non-radioactive methods for the detection of trace amines in biological samples have limited their investigation in humans. However, the recent identification of a new, large family of G protein-coupled receptors, some of which bind and are activated by trace amines, has focused renewed attention on these compounds.