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 heter-ogeneously distributed and present in synaptosomes, and it is synthesized and degraded very quickly. If deuterium is substituted for hydrogen on the α 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.
KeywordsLocus Coeruleus Phenylacetic Acid Deuterium Isotope Effect Trace Amine Deuterium Substitution
Unable to display preview. Download preview PDF.
- Boulton AA, Juorio AV (1982) Brain trace amines. In: Lajtha A (ed) Handbook of neu-rochemistry, vol 1. Plenum Press, New York, p 189.Google Scholar
- Durden DA, Boulton AA (1982a) Mass spectrometric analysis of some neurotransmitters and their precursors and metabolites. In: Lajtha A (ed) Handbook of neurochemistry, vol 2. Plenum Press, New York, p 397.Google Scholar
- Dyck LE, Juorio AV, Durden DA, Boulton AA (1988) Effect of chronic deuterated and non-deuterated phenelzine on rat brain monoamines and MAO. Naunyn-Schmiede-bergs Arch Pharmacol 337: 279–283.Google Scholar
- Harris J, Trivedi S, Ramakrishna BL (1988) A contribution to the neuromodulatory/ neurotransmitter role of the trace amines. In: Boulton AA, Juorio AV, Downer RGH (eds) Trace amines: comparative and clinical neurobiology. Humana Press, Clifton, New Jersey, p 213.Google Scholar
- Juorio AV, Paterson IA (1988) The effect of nigral stimulation on the accumulation of PE in the rat striatum. Soc Neurosci Abstracts 14: 1074 (433.3).Google Scholar
- Juorio AV (1988) Brain trace amines: mapping studies and effects of mesencepahlic lesions. In: Boulton AA, Juorio AV, Downer RGH (eds) Trace amines: comparative and clinical neurobiology. Humana Press, Clifton, New Jersey, p 157.Google Scholar
- Paterson IA, Juorio AV, Zhu MY (1989) The effect of α-methyl-p-tyrosine on the concentration of β-phenylethylamine in the rat striatum. Soc Neurosci Meeting, Phoenix, Arizona.Google Scholar