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At least 19 recordsLinked to original sources
PubMed1986

Discriminative stimulus properties of beta-phenylethylamine, deuterated beta-phenylethylamine, phenylethanolamine and some metabolites of phenylethylamine in rodents.

The discriminative stimulus (cue) properties of phenylethylamine (PEA) were analysed in rodents in a conventional two lever FR10 operant drug discrimination task. Rats trained to discriminate phenylethylamine at 30 mg/kg showed complete dose-related generalization to PEA and to two potential PEA metabolites: phenylethanolamine (PEOH) and N-Methyl PEA (NMPEA). Only partial (50%) generalization was seen with N-Methylphenylethanolamine (NMPEOH), another potential PEA metabolite. The specificity of PEA's action as a discriminative stimulus was demonstrated by the finding that fenfluramine, a substituted phenylethylamine, failed to generalize to PEA even at high doses with marked behavioural effects which are known to have discriminative stimulus properties themselves. These data suggest that NMPEA and PEOH may be functionally important active metabolites of PEA, particularly if the major pathway of PEA metabolism to phenylacetic acid under the influence of MAO Type B is for any reason impaired. A long acting deuterium substituted form of PEA (alpha, alpha, d2 PEA), which is resistant to metabolism by MAO, produced complete dose-related generalization to the PEA cue but was more potent than PEA, due presumably to its resistance to metabolism by MAO. Deuterated PEA may therefore be a useful agent to use in future studies of the PEA cue, because the discriminability of PEA itself appears to be low due to its very rapid metabolism in vivo.

Animals↗
PubMed1987

Pharmacokinetic and neurochemical studies on N-propargyl-2-phenylethylamine, a prodrug of 2-phenylethylamine.

Pharmacokinetic and neurochemical properties of N-propargyl-2-phenylethylamine, a known MAO inhibitor and a potential prodrug of the bioactive trace amine, 2-phenylethylamine, were studied in rats. Intraperitoneal (i.p.) administration of N-propargyl-2-phenylethylamine produced marked elevations in 2-phenylethylamine levels in rat brain, blood and liver; these levels remained significantly above controls for more than 4 h. Neurochemical studies showed the drug to be a preferential MAO-B inhibitor at a dose of 0.1 mmol/kg (i.p.). This selectivity was much more pronounced in liver than in brain. N-Propargyl-2-phenylethylamine produced a significant decrease in whole brain concentrations of noradrenaline, dopamine and DOPAC, but they returned to control values by 3 h after drug administration. Concentrations of 5-HT were unaffected, while 5-HIAA and HVA concentrations increased significantly above controls. Results indicate that N-propargyl-2-phenylethylamine is a prodrug of 2-phenylethylamine and a potentially useful pharmacological tool with which to study the functional role of 2-phenylethylamine in the mammalian central nervous system.

Animals↗
PubMed1982

Self-administration of the endogenous trace amines beta-phenylethylamine, N-methyl phenylethylamine and phenylethanolamine in dogs.

beta-Phenylethylamine and phenylethanolamine are biogenic amines structurally related to amphetamine which are known to occur endogenously in trace amounts in mammalian brain. The purpose of the present experiments was to determine whether these endogenous biogenic amines, like amphetamine, have reinforcing properties. Dogs surgically prepared with i.v. catheters were permitted 4-hr daily access to i.v. infusions of beta-phenylethylamine, phenylethanolamine, N-methylphenylethylamine, cocaine or d-amphetamine under a fixed-ratio one-response schedule of reinforcement. In dogs which had not previously self-administered drugs, the number of infusions self-administered per session of beta-phenylethylamine, N-methyl phenylethylamine and cocaine increased above that for saline typically within 5 to 10 sessions. Increases in the number of injections per session were observed in only two of five dogs with phenylethanolamine, and in only three of five dogs with d-amphetamine within as many as 20 to 40 sessions. Does-effect curves were determined in dogs which had been trained previously to self-administer drug and whose daily drug intake was stable. The relative potencies of these compounds in maintaining self-administration behavior during the 4-hr session were d-amphetamine greater than cocaine greater than phenylethanolamine greater than or equal to N-methyl phenylethylamine greater than or equal to beta-phenylethylamine. These data indicate that the endogenous trace amines beta-phenylethylamine, phenylethanolamine and the N-methyl homolog of beta-phenylethylamine can function as reinforcers and are compatible with hypotheses that they may play a physiological role in the reinforcement process or in neuropsychiatric disorders.

2-Hydroxyphenethylamine↗
PubMed1977

Phenylethylamine and cerebral blood flow. Possible involvement of phenylethylamine in migraine.

Phenylethylamine can initiate migraine-type headaches in susceptible individuals. Migraine sufferers have a reduced ability to deaminate all monoamines, but particularly phenylethylamine. Phenylethylamine readily crosses the blood-brain barrier and thus could be a mediator of the cerebrovascular disturbances seen in migraine attacks. Cerebral blood flow was measured in 15 anesthetized baboons by the intracarotid 133Xe clearance technique. Phenylethylamine (4 x 10(-7) moles.kg-1min-1) produced significant increases in cerebral blood flow (36 percent) and cerebral oxygen consumption (45 percent) during the first 40 minutes of infusion. In contrast, an increased phenylethylamine concentration (2 X 10(-6) moles.kg-1min-1) constricted the cerebral bed (cerebral blood flow reduced by 28 percent). The response of the cerebral circulation to hypercapnia was preserved during the infusion. Phenylethylamine thus is capable of producing in an experimental animal a pattern of cerebrovascular events similar to those seen in migraine.

Animals↗
PubMed1986

In vivo release of endogenous dopamine from rat caudate nucleus by beta-phenylethylamine and alpha,alpha,-dideutero-beta-phenylethylamine.

The release of endogenous dopamine (DA) has been measured in the rat striatum following the intracardial administration of various doses of beta-phenylethylamine (PEA) or alpha,alpha-dideutero-beta-phenylethylamine (deuterated PEA). The release was significantly increased for a period of approximately 15 minutes by a dose of 25 mg/kg PEA. Both the dose required to stimulate DA release and the duration of the effect were in good agreement with previously reported behavioral and locomotor effects of administered PEA. When the animals were given 25 mg/kg of deuterated PEA, the increase in DA release was both longer lasting and significantly greater in magnitude than that observed in response to the non-deuterated amine. The results of these experiments provide direct evidence that DA release is stimulated by amounts of PEA known to cause behavioral effects and locomotor activity in rats, and suggest that these effects are likely to be mediated, at least in part, by DA.

Animals↗
PubMed1987

N,N-dipropargyl-2-phenylethylamine, a potential prodrug of 2-phenylethylamine: neurochemical and neuropharmacological studies in rat.

An evaluation of N,N-dipropargyl-2-phenylethylamine (DPGPEA) as a prodrug to increase brain levels of 2-phenylethylamine (PEA) was conducted in rats. A 0.1 mmol/kg (IP) dose of DPGPEA was administered and produced marked elevations of PEA levels in brain, liver and blood which were sustained for several hours. Ex vivo MAO inhibition data indicated DPGPEA to be an inhibitor of MAO-B, although the effect was much weaker than seen with tranylcypromine or pargyline. DPGPEA caused brain noradrenaline, dopamine and 3,4-dihydroxyphenylacetic acid levels to temporarily decrease significantly below controls. Concomitant increases in homovanillic acid and 5-hydroxyindole-3-acetic acid levels suggest that the PEA or N-propargylPEA formed and/or DPGPEA itself have significant effects on release and reuptake of neurotransmitters. DPGPEA was also shown to be metabolized to N-propargyl-PEA, another prodrug of PEA, in vivo.

Animals↗
PubMed1999

Synthesis and SAR of 1-alkyl-2-phenylethylamine derivatives designed from N,N-dipropyl-4-methoxy-3-(2-phenylethoxy)phenylethylamine to discover sigma(1) ligands.

The synthesis and structure-activity relationships (SAR) of 1-alkyl-2-phenylethylamine derivatives 5-8 designed from N, N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (1, NE-100) are presented. The SAR between compound 1 and 1-alkyl-2-phenylethylamine derivatives suggested that the alkyl group on the 1-position carbon of 2-[4-methoxy-3-(2-phenylethyl)phenyl]ethylamine derivatives played the role of one of the propyl groups on the aminic nitrogen of compound 1. (-)-N-Propyl-1-butyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylam ine hydrochloride ((-)-6d, NE-537) and (-)-N-propyl-1-(3-methybutyl)-2-[4-methoxy-3-(2-phenylethoxy )phenyl]e thylamine hydrochloride ((-)-6i, NE-535), typical compounds in this series, have potent and selective sigma(1) affinity.

Alkylation↗
PubMed2005

[(S)-1-Carbamoylethyl]bis(dimethylglyoximato-kappa2N,N')[(S)-1-phenylethylamine]cobalt(III) and bis(dimethylglyoximato-kappa2N,N')[(R)-1-(N-methylcarbamoyl)ethyl][(R)-1-phenylethylamine]cobalt(III) monohydrate.

The title complexes, [Co(C3H6NO)(C4H7N2O2)2(C8H11N)] and [Co(C4H8NO)(C4H7N2O2)2(C8H11N)].H2O, were resolved from [(RS)-1-carbamoylethyl]bis(dimethylglyoximato)[(S)-1-phenylethylamine]cobalt(III) and bis(dimethylglyoximato)[(RS)-1-(N-methylcarbamoyl)ethyl][(R)-1-phenylethylamine]cobalt(III), respectively, and their crystal structures were determined in order to reveal the absolute configuration of the major enantiomer produced in the photoisomerization of each series of 2-carbamoylethyl and 2-(N-methylcarbamoyl)ethyl cobaloxime complexes.

Carbamates↗
PubMed1987

Neuropharmacological and neurochemical properties of N-(2-cyanoethyl)-2-phenylethylamine, a prodrug of 2-phenylethylamine.

1 N-(2-cyanoethyl)-2-phenylethylamine (CEPEA) was examined as a possible prodrug of 2-phenylethylamine (PEA). 2 Pharmacokinetics of PEA and CEPEA were investigated in rat brain, blood and liver by gas chromatography with electron-capture detection (GC-ECD). Interactions of PEA and CEPEA with putative neurotransmitter amines were investigated by use of high performance liquid chromatography with electrochemical detection (h.p.l.c.-e.c.). 3 Administration of PEA caused transient increases in PEA concentrations which decreased rapidly in brain and blood and at a slower rate in liver. Administration of CEPEA caused sustained elevations of PEA concentrations and elimination of PEA was markedly decreased in these tissues relative to the situation after administration of PEA itself. 4 Administration of CEPEA caused more prolonged decreases in brain noradrenaline, dopamine and 5-hydroxytryptamine concentrations than those observed after PEA administration, although values increased to control levels eventually.

Animals↗
PubMed1984

Characteristics of analgesia induced by noncatecholic phenylethylamine derivatives: possible involvement of endogenous opioid peptides and serotonin in phenylethylamine analog-induced analgesia.

Characteristics of the analgesic action of phenylethylamine derivatives, amphetamine, phenylethylamine (PEA), hydroxyphenylethylamine (OHPEA) and hydroxyphenylalanine (OHF), were examined. Pain threshold of mice was measured by using the hot plate method. OHPEA (50 mg/kg), amphetamine (0.5-8 mg/kg) or PEA (50 mg/kg) produced an analgesic effect in the absence of MAO inhibitor, and the analgesia was reversed by naloxone (5 mg/kg) or reserpine (2 mg/kg x 2). Ten mg/kg of PEA, 250 mg/kg of OHF and 10 mg/kg of OHPEA could not produce detectable analgesia, but they revealed analgesic activity when mice were pretreated with pargyline (100 mg/kg). Analgesia induced by a combined use of PEA, OHF or OHPEA with pargyline was inhibited by naloxone or p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis. Amphetamine-induced analgesia was also blocked by PCPA. Analgesia induced by PEA or OHPEA was blocked by methysergide (2 mg/kg). From the above findings, it was concluded that PEA, OHPEA, OHF and amphetamine possess similar characteristics in their analgesic action, and their analgesic actions involve the participation of endogenous serotonin and endogenous opioid peptides.

2-Hydroxyphenethylamine↗
PubMed1988

Characteristics of antinociception induced by noncatecholic phenylethylamine derivatives: the relation of endogenous norepinephrine to phenylethylamine analog-induced antinociception.

Characteristics of the antinociceptive action of phenylethylamine derivatives, amphetamine, beta-phenylethylamine (PEA) and beta-hydroxyphenylethylamine (OHPEA), were examined. The pain threshold of mice was measured by using the hot plate method. Intraperitoneal administration of alpha-methyl-p-tyrosine inhibited antinociception induced by PEA and OHPEA, and intracisternal administration of norepinephrine increased antinociception induced by PEA and OHPEA. Intracisternal administration of phentolamine inhibited the antinociception induced by PEA derivatives. The levels of norepinephrine and normetanephrine in the brain were determined by using HPLC. PEA derivatives decreased norepinephrine in the brain and tended to increase normetanephrine at 15 min after the administration of PEA derivatives. These findings indicate that PEA derivatives cause the release of norepinephrine in the central nervous system, and the released norepinephrine induces antinociception.

2-Hydroxyphenethylamine↗
PubMed1996

Action of beta-phenylethylamine and related amines on nigrostriatal dopamine neurotransmission.

The present paper describes the effect of beta-phenylethylamine and its metabolites phenylethanolamine, tyramine, acetyl-phenylethylamine and phenylacetaldehyde on the dopaminergic nigrostriatal system. The rotational behavioural response to the i.v. injection of these drugs was quantified in animals with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine system. Only beta-phenylethylamine and acetyl-phenylethylamine induced rotations ipsilateral to the side of the brain lesion. None of the compounds under study stimulated contralateral rotations. Acetyl-phenylethylamine was 90% less active than beta-phenylethylamine. After beta-phenylethylamine injection all animals (16/16) showed ipsilateral rotations. The dose-response curve showed that at doses as low as 1.75 mg/kg ipsilateral turns increase, with a dose-related rotational response between 1.75 mg/kg and 11.66 mg/kg, no differences being found at doses between 11.66 and 29.16 mg/kg. Rotations began a few seconds after beta-phenylethylamine injection. The highest response was found 30-60 s after the injection. The duration of the response was dose-related (4 min for the 3.5 mg/kg doses). The inhibition of dopamine-beta-hydroxylase activity with [1-3,5-difluorobenzyl)imidazole-2-thiol (SKF102698) did not modify the rotational response to beta-phenylethylamine. The inhibition of type B monoamine oxidase activity with l-deprenyl induced a slight increase in the ipsilateral rotational response to beta-phenylethylamine. The inhibition of tyrosine hydroxylase activity with alpha-methyl-p-tyrosine decreased the rotational response to beta-phenylethylamine. The dopamine receptor antagonist, haloperidol, completely blocked the ipsilateral rotational response to beta-phenylethylamine. The blocking of dopamine uptake into storage vesicles with reserpine increased the rotational action of beta-phenylethylamine. Taken together, the data suggest that, at low doses, beta-phenylethylamine stimulates the release of dopamine from the cytoplasmic pool and behaves as a dopamine receptor agonist with a very rapid and brief action.

Amines↗
PubMed2001

beta-Phenylethylamine modulates acetylcholine release in the rat striatum: involvement of a dopamine D(2) receptor mechanism.

We examined the effects of beta-phenylethylamine on striatal acetylcholine release in freely moving rats using in vivo microdialysis. beta-Phenylethylamine at 12.5 mg/kg, i.p. did not affect acetylcholine release in the striatum, whereas 25 and 50 mg/kg, i.p. immediately induced an increase in acetylcholine release in the striatum at 15-45 min. This increase following intraperitoneal administration of beta-phenylethylamine (25 mg/kg) was not affected by locally applied SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine, 10 microM), a dopamine D(1) receptor antagonist, nor by raclopride (10 microM), a dopamine D(2) receptor antagonist. The increased release of acetylcholine induced by beta-phenylethylamine was suppressed by local infusion of tetrodotoxin (1 microM). In contrast, the extracellular acetylcholine level in the striatum was significantly decreased by local application of beta-phenylethylamine (10 and 100 microM) in the striatum via a microdialysis probe. The decrease was completely blocked by local co-application of raclopride (10 microM). The beta-phenylethylamine-induced decrease in striatal acetylcholine release was not affected by co-perfusion with SCH-23390 (10 microM). These results indicate that systemic administration of beta-phenylethylamine increases acetylcholine release, whereas locally applied beta-phenylethylamine decreases striatal acetylcholine release in freely moving rats. Furthermore, the dopaminergic system, through the dopamine D(2) receptor, is involved in the locally applied beta-phenylethylamine-induced decrease in acetylcholine in the striatum.

Acetylcholine↗
PubMed1988

Reciprocal changes in striatal dopamine and beta-phenylethylamine induced by reserpine in the presence of monoamine oxidase inhibitors.

Recent studies have demonstrated that selective monoamine oxidase inhibition may induce changes in brain beta-phenylethylamine availability following lesions. The present study used this approach to re-assess the possible effects of reserpine on striatal concentrations of beta-phenylethylamine and of other amines and selected metabolites. Mice were injected with pargyline (2,200 mg kg-1, 4 h), clorgyline (2 mg kg-1, 2 h) or (-)deprenyl (2 mg kg-1, 2 h) alone or in combination with reserpine (1, 10 mg kg-1, 2 h). Increases in beta-phenylethylamine accumulation were observed in the presence of both (-)deprenyl or pargyline respectively after reserpine except in the case of combined 200 mg kg-1 of pargyline plus 1 mg kg-1 of reserpine. In this condition, a minimal dopamine decrease was observed (to 80% of the concentration of pargyline-treated controls). Increases in beta-phenylethylamine concentration were not observed with reserpine alone (1 or 10 mg kg-1). In the latter condition, the concentrations of beta-phenylethylamine remained at control values due to the activity of monoamine oxidase B. Changes in p-tyrosine, 5-hydroxytryptamine or tryptophan did not consistently accompany increases in beta-phenylethylamine accumulation. Increased beta-phenylethylamine accumulation was always accompanied by the decreases in dopamine induced by reserpine in mice with either non-selective (200 mg kkg-1 pargyline) or type B monoamine oxidase inhibition (2 mg kg-1 pargyline or deprenyl). These data suggest that although the changes in beta-phenylethylamine accumulation may not be due simply to p-tyrosine availability they are related to dopamine levels in the intact striatum.

Animals↗
PubMed1993

Down-regulation of beta-adrenergic and dopaminergic receptors induced by 2-phenylethylamine.

1. The effects of chronic administration (28 days s.c. via Alzet osmotic minipumps) of 2-phenylethylamine.HCl (10 mg kg-1 per day) and/or (-)-deprenyl.HCl (1 mg kg-1 per day) on dopamine and noradrenaline receptor subtypes have been measured in rat brain. 3H-CGP 12177 was used to label beta-adrenoceptors; 3H-spiperone and 3H-SCH 23390 were used to label D2-like and D1-like receptors. 2. Total cortical beta-adrenoceptor density was reduced by (-)-deprenyl but not 2-phenylethylamine alone. Combined administration of 2-phenylethylamine and (-)-deprenyl resulted in a significantly larger decrease than (-)-deprenyl alone. Subtype density analysis by competition experiments with ICI 89406 revealed that the (-)-deprenyl effect in cortex was due to a decrease in beta 1-adrenoceptor density. The combination of 2-phenylethylamine and (-)-deprenyl resulted in a significant decrease in both cortical beta 1- and cortical beta 2-adrenoceptors. Cerebellar beta-adrenoceptor density was not altered by the present drug treatments. The Kd values for total beta-adrenoceptor densities and Ki values for beta-adrenoceptor subtype densities were not altered by drug treatment in either cortex or cerebellum. 3. Administration of 2-phenylethylamine and of (-)-deprenyl resulted in a decrease in the density of D1-like 3H-SCH 23390 but not D2-like 3H-spiperone binding to dopamine receptors in the striatum. The effects of combined 2-phenylethylamine and (-)-deprenyl treatment on 3H-SCH 23390 binding were additive. These drug treatments did not alter Kd values for these binding sites. 4. The down-regulation of catecholamine receptors following chronically increased availability of 2-phenylethylamine may be due to the catecholamine releasing or uptake blocking effects of this amine. These effects may also be attributable to a direct neuromodulatory action of 2-phenylethylamine on catecholamine receptors. 5. The parallels between effects of increased 2-phenylethylamine availability and effects of administration of MAO inhibitor antidepressants on catecholamine receptor systems indicate that this substrate for MAO may mediate some of the effects of MAO inhibitor antidepressants.

Animals↗
PubMed1985

Behavioral and neurochemical effects of deprenyl and beta-phenylethylamine in Wistar rats.

The effects of 1-deprenyl (1-16 mg kg-1, 3.5 hr) on brain levels of endogenous beta-phenylethylamine were assessed in animals under three conditions: (1) experience of lateral hypothalamic self-stimulation; (2) electrode implantation but no self-stimulation experience; (3) no surgical intervention. The increase in striatal levels of beta-phenylethylamine with 1-deprenyl treatment was attenuated in the self-stimulation condition relative to conditions (2) and (3). This differential effect of 1-deprenyl was not observed at the level of the hypothalamus. Administration of 1-deprenyl did not affect self-stimulation behavior. Equivalent analysis of beta-phenylethylamine levels was carried out using animals injected with beta-phenylethylamine (0.5-4 mg kg-1, 0.5 hr 1P and 1-deprenyl (4 mg kg-1, 3.5 hr sc). Injected beta-phenylethylamine with deprenyl pretreatment increased self-stimulation rates; concomitant striatal levels of approximately 190 ng g-1 of beta-phenylethylamine were observed and were associated with increased brainstem 5-HIAA but no change in striatal HVA, indicating possible involvement of 5-HT in this response to beta-phenylethylamine. It is proposed that experience of electrical hypothalamic stimulation may alter endogenous striatal beta-phenylethylamine metabolism, possibly via an alteration of mechanisms governing synthesis and/or catabolism.

Animals↗