Phenylethylamine in the CNS: effects of monoamine oxidase inhibiting drugs, deuterium substitution and lesions and its role in the neuromodulation of catecholaminergic neurotransmission.

Phenylethylamine is present in brain in tiny quantities, it is heterogeneously distributed and present in synaptosomes, and it is synthesized and degraded very quickly. If deuterium is substituted for hydrogen on the alpha carbon of the side chain then it exhibits profound isotope effects to MAO and its penetration and persistence in the brain is considerably enhanced. In the presence of MAO-B inhibitors treatment with reserpine causes reciprocal changes to PE and DA suggesting a functional relationship between them and after unilateral lesions of the substantia nigra an ipsilateral reduction in striatal PE is seen suggesting again a co-relationship with DA. Following iontophoresis PE has been shown to exhibit indirect sympathomimetic effects but in addition when applied at low currents concurrently with DA or NA it causes post synaptically a substantial potentiation in the actions of the latter amines. As a result of this and other data PE has been proposed to be a neuromodulator of catecholaminergic transmission.