Rat Brain-Uptake Index for Phenylethylamine and Various Monomethylated Derivatives

  title={Rat Brain-Uptake Index for Phenylethylamine and Various Monomethylated Derivatives},
  author={Aron David Mosnaim and Owen H. Callaghan and Thomas J Hudzik and Marion E. Wolf},
  journal={Neurochemical Research},
Phenylethylamine and its monomethylated derivatives p-methylphenylethylamine, α-methylphenylethylamine, phenylethylamine itself, N-methylphenylethylamine, o-methylphenylethylamine, and β-methylphenylethylamine, readily cross the blood-brain barrier showing a brain-uptake index (%) ± SD (water considered 100 %), of 108 ± 11, 98 ± 14, 83 ± 6, 78 ± 11, 62 ± 7 and 56 ± 6, respectively (injection of tritiated water and 100 μg standard amine, which was measured by gas-liquid chromatography). Similar… 
β-Phenylethylamine and various monomethylated and para-halogenated analogs. Acute toxicity studies in mice
Phenylethylamine’s acute toxic effects in a population of adult Swiss male albino mice are significantly increased by para-position aromatic ring halogenation and variation between the various p-halogenatedPEAs fell within a relatively narrow range.
Analgesic Effects of β-Phenylethylamine and Various Methylated Derivatives in Mice
Individual compound’s antinociceptive properties were reliably increased by P, decreased by reserpine or haloperidol, and remained essentially unchanged after naloxone (N) administration suggesting the involvement of catecholamines, but not opioid peptides, in their observed analgesic effects.
Pharmacological characterization of a high-affinity p-tyramine transporter in rat brain synaptosomes
This work identifies Organic Cation Transporter 2 (OCT2; SLC22A2) as mediating high affinity uptake of p-tyramine at physiologically relevant concentrations and confirms the presence of OCT2 protein in synaptosomes, the first identification of a high affinity neuronal transporter for p-Tyramine.
Behavioral Effects of &bgr;-Phenylethylamine and Various Monomethylated and Monohalogenated Analogs in Mice Are Mediated by Catecholaminergic Mechanisms
A number of as yet little studied monomethylated and monohalogenated PEA analogs share a similar behavioral profile with PEA and AMPH, and Behavioral changes observed appear to be, at least in part, mediated by catecholaminergic mechanism as they are modulated by drugs known to influence catechlamine activity.
Potential of Ligands for Trace Amine-Associated Receptor 1 (TAAR1) in the Management of Substance Use Disorders
Selective and potent engineered TAAR1 ligands serve as invaluable tools for the investigation ofTAAR1 functions and display significant potential for the development of TAar1-based pharmacotherapies for the treatment of substance use disorders.
Trace Amines and Their Receptors
In the brain, TAAR1 acts as a rheostat of dopaminergic, glutamatergic, and serotonergic neurotransmission and has been identified as a novel therapeutic target for schizophrenia, depression, and addiction, and in the periphery,TAAR1 regulates nutrient-induced hormone secretion, suggesting its potential as a Novel therapeutic targets for diabetes and obesity.
Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection
It is demonstrated that the NT-lipidoid formulation not only facilitates cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination.


2-Phenylethylamine as a possible mediator for Δ9-tetrahydrocannabinol-induced stimulation
IF neuroamines modulate perception and affect, as implied in much of the literature, the behavioural effects of marihuana may be mediated by alterations of brain amine mechanisms, Even in large doses
Comparative effects of amphetamine, phenylethylamine and related drugs on dopamine efflux, dopamine uptake and mazindol binding.
  • E. Parker, L. Cubeddu
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1988
It is proposed that AMPH-like drugs increase DA efflux from a single cytoplasmic pool maintained by DA synthesis and spontaneous and drug-induced efflux of DA from storage vesicles.
Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor.
The discovery and pharmacological characterization of a rat G protein-coupled receptor that stimulates the production of cAMP when exposed to the trace amines p-tyramine, beta-phenethylamine, tryptamine, and octopamine and the discovery that amphetamines are potent rTAR1 agonists suggests that the effects of these widely used drugs may be mediated in part by this receptor as well as their previously characterized targets, the neurotransmitter transporter proteins.
Determination of regional distributions of phenylethylamine andmeta-andpara-tyramine in rat brain regions and presence in human and dog plasma by an ultra-sensitive negative chemical ion gas chromatography-mass spectrometric (NCI-GC-MS) method
Using a new ultrasensitive method the trace biogenic amines, phenylethylamine, meta-tyramine andpara-Tyramine have been quantitated in brain regions obtained from a single rat indicating that MAO-B is not present in plasma in significant quantities.
β-Phenylethylamine Alters Monoamine Transporter Function via Trace Amine-Associated Receptor 1: Implication for Modulatory Roles of Trace Amines in Brain
  • Zhihua Xie, G. Miller
  • Biology, Chemistry
    Journal of Pharmacology and Experimental Therapeutics
  • 2008
Results reveal that β-PEA alters monoamine transporter function via interacting with TAAR1 but not monoamine autoreceptors, which may reveal a common mechanism by which trace amines exert modulatory effects on monoamine transporters in brain.
An enzymatic isotopic assay for the measurement of β‐phenylethylamine in brain, with a sensitivity of 100‐200 pg, has been developed and the endogenous β‐ Phenylalanine content in the rat brain has been determined.
Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators
Previous studies showing responses to physiologically relevant concentrations of trace amines are reviewed, along with those showing a reciprocal relationship between trace amine levels and fluctuations in basal monoaminergic tone, and it is hypothesized that the traceAmines function as endogenous neuromodulators of classical monoamine neurotransmitters.
Degradation Kinetics by MAO of PEA Derivatives. A Model for the Molecular Basis of their Analgesic and Behavioral Effects
The classical endogenous noncatecholic phenylethylamines, phenylethylamine (PEA), phenylethanolamine, p-tyramine and p-octopamine appear to be involved in peripheral and central nervous system
Identification of trace-amine-associated receptors (TAAR) in the rat aorta and their role in vasoconstriction by β-phenylethylamine
The presence of TAar-1 suggests that vasoconstriction may be via these receptors; however, the potency order differed from that reported for transfected cells expressing rat TAAR-1.
Trace amines: Identification of a family of mammalian G protein-coupled receptors
Using a degenerate PCR approach, 15 G protein-coupled receptors (GPCR) from human and rodent tissues are identified and it is demonstrated that two of these receptors bind and/or are activated by trace amines.