from NIH PubMed

Phenylethylamine can act as an endogenous amphetamine in some patients

In brain capillary endothelium and catecholaminergic terminals a single decarboxylation step effected by aromatic amino-acid decarboxylase converts phenylalanine to phenylethylamine, at a rate comparable to that of the central synthesis of dopamine. Phenylethylamine, however, is not stored in intra-neuronal vesicles and is rapidly degraded by monoamine oxidase-B. Despite its short half-life, phenylethylamine attracts attention as an endogenous amphetamine since it can potentiate catecholaminergic neurotransmission and induce striatal hyperreactivity. Subnormal phenylethylamine levels have been linked to disorders such as attention deficit and depression; the use of selegiline (Deprenyl) in Parkinson’s disease may conceivably favour recovery from deficient dopaminergic neurotransmission by a monoamine oxidase-B inhibitory action that increases central phenylethylamine. Excess phenylethylamine has been invoked particularly in paranoid schizophrenia, in which it is thought to act as an endogenous amphetamine and, therefore, would be antagonized by neuroleptics. The importance of phenylethylamine in mental disorders is far from fully elucidated but the evolution of phenylethylamine concentrations in relation to symptoms remains a worthwhile investigation for individual psychotic patients.

A review of the literature indicates that brain phenylethylamine (PEA) may be a neuromodulator of aminergic synapses and that it promotes energy, elevates mood, and favors aggression. Phenylacetic acid, the main metabolite of PEA, is decreased in the biological fluids of depressed subjects and schizophrenic subjects and is increased in schizoaffective subjects. The administration of PEA or of its precursor L-phenylalanine improves mood in depressed patients treated with a selective monoamine oxidase B inhibitor. The authors speculate that studies of PEA metabolism may have diagnostic value and that PEA administration may be therapeutic in selected depressed patients.

from NIH PubChem

Mechanism of Action

Systemic administration of beta-phenylethylamine increases acetylcholine release, whereas locally applied beta-phenylethylamine decreases striatalacetylcholine release in freely moving rats. Furthermore, the dopaminergic system, through the dopamine D(2) receptor, is involved in the locally applied beta-phenylethylamine-induced decr in acetylcholine in the striatum. Abstract: PubMed

Kato M et al; Eur J Pharmacol 418 (1-2): 65-71 (2001)

2-Phenylethylamine (PE) is an endogenous brain amine which produces sympathomimetic responses and potentiates cortical neuron responses tonoradrenaline (NA)… . It is probable that the ability of PE to modulate neuronal responses to NA does not involve the presynaptic NA terminal or endogenous NA and it is likely that PE acts directly to increase the efficacy of NA. These findings are consistent with the hypothesis that the physiological role of PE is to modulate catecholaminergic transmission within the central nervous system. Abstract: PubMed

Paterson IA; Neurochem Res 18(12): 1329-36 (1993)

… These results suggest that phenylethylamine-HCl (PEA) and methamphetamine-HCl (MAP) increase the amplitude of the monosyaptic reflex /in spinalized rats transected at C1/ by releasing noradrenaline from the terminals of descending noradrenergic fibers, and that PEA, an endogenous trace amine, has a mechanism of action similar to that of MAP. Abstract: PubMed

Ono H et al; Jpn J Pharmacol 55(3): 359-66 (1991)

Both PEA and antidepressants induced a reduction in the behavioral response to the beta 2 adrenoceptor agonist salbutamol. Radioligand binding measurements revealed that 28 day administration of PEA in combination with the type B MAOI (-)-deprenyl results in a decrease in the density of beta 1 adrenoceptors but not beta 2 adrenoceptors in rat cerebral cortex and cerebellum. (-)-Deprenyl alone also induced a significant decrease in beta 1-adrenoceptors but when PEA was added to this treatment there was a further decrease in beta 1-adrenoceptor density. Only changes in beta 1 adrenoceptor density were evident following 28 day administration of MAOI antidepressants. PEA also induced a decrease in the density of D1-like dopamine (DA) receptors in the rat striatum. MAOI antidepressants induced a decrease in the density of both D1-like and D2-like DA receptors. These data are discussed in terms of a possible role of PEA-catecholamine interactions in antidepressant drug action. Abstract: PubMed

Paetsch PR, Greenshaw AJ; Neurochem Res 18(9): 1015-22 (1993)

Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ beta-Phenylethylamine (PEA) is a trace neuroactive amine implicated in the regulation of the hypothalamic-pituitary-adrenal (HPA) response to stress. To test this hypothesis, effects of subchronic levels of PEA (50 mg/kg/day … for 10 days) on the corticotroph function were studied. PEA treatment induces: (i) a significant incr of corticotrophin releasing hormone (CRH) immunoreactivity in the median eminence (ME), as measured by semi-quantitative immunofluorescence labeling techniques, (ii) a significant incr in CRH mRNA levels in paraventricular nuclei, as detected by in situ hybridization, & (iii) an incr in plasma adreno-corticotrophin hormone (ACTH) & corticosterone levels in responses to stress. PEA treatment has no effect on the number of binding sites & on the dissociation constant of the glucocorticoid receptors in any structure studied. Results of thedexamethasone suppression test were similar in PEA- & saline-treated rats. Taken together, these results suggest that PEA treatment stimulated the HPA axis activity levels directly via the CRH hypothalamic neurons, without altering the negative feed back control exerted by the glucocorticoids. Abstract: PubMed

Kosa E et al; Pharmacol Biochem Behav 67 (3): 527-35 (2000)

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ The effects of chronic admin of antidepressant drugs & 2-phenylethylamine on beta-adrenoceptor function were assessed. MAO inhibitors (phenelzine sulfate, 5 or 10 mg/kg/day, & (-)-deprenyl HCl, 1 mg/kg/day) & 2-phenylethylamine HCl (10 mg/kg/day) were administered to male Sprague-Dawley rats… . On days 21 & 22, the motor-suppressant actions of …salbutamol hemisulfate (3 mg/kg ip after 15 min) were assessed as a measure of beta-adrenoceptor sensitivity. On day 28, the animals were killed, & their brains were used for the measurement of monoamine oxidase activity & concns of 2-phenylethylamine, an endogenous amine & a metabolite of phenelzinePhenelzine sulfate at 10 mg/kg/day …& the combination of (-)-deprenyl & 2-phenylethylamine resulted in a decr in the response to salbutamol /and/ …substantial increases in brain 2-phenylethylamineconcns. …These results support the proposal that 2-phenylethylamine may, at least in part, mediate the effects of phenelzine on beta-adrenoceptor function.Abstract: PubMed

Paetsch PR et al; J Pharm Sci 82 (1): 22-4 (1993)