Effects of tranylcypromine on the concentrations of some trace amines in the diencephalon and hippocampus of the rat

Philips, S. R.; Baker, Glen B.; McKim, H.R.

doi:10.1007/bf01953756

“…The brain concentrations of PEA obtained after administration ofCEPEA are similar to or greater than those reported after administration of MAO inhibitors (Boulton et al, 1973;Philips & Boulton, 1979;Philips et al, 1980;Baker et al, 1984). The administration of CEPEA did not markedly inhibit MAO activity, and this study demonstrates the feasibility of using a prodrug to increase the brain PEA concentrations.…”

Section: Discussionsupporting

confidence: 70%

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

Baker

¹

,

Coutts

²

,

Rao

³

1987

British J Pharmacology

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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.

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“…In summary, CEPEA administration caused sustained elevation of rat brain, blood and liver PEA concentrations, thus acting as a prodrug. The brain concentrations of PEA obtained after administration ofCEPEA are similar to or greater than those reported after administration of MAO inhibitors (Boulton et al, 1973;Philips & Boulton, 1979;Philips et al, 1980;Baker et al, 1984). The administration of CEPEA did not markedly inhibit MAO activity, and this study demonstrates the feasibility of using a prodrug to increase the brain PEA concentrations.…”

Section: Discussionsupporting

confidence: 70%

Untitled

1987

British J Pharmacology

0

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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.

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“…B. TA measurements were recorded 6 h after intraperitoneal (i.p.) injection of TCP/PLZ (Baker et al 1984), but peak TA concentrations may well have subsided by then: Philips et al (1980) demonstrated that, following i.p. TCP injection in the rat model, TA levels in both hippocampus and diencephalon peaked after roughly 45-90 min.…”

Section: Framing the Discussionmentioning

confidence: 99%

The trace amine theory of spontaneous hypertension as induced by classic monoamine oxidase inhibitors

Eynde¹

2021

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The classic monoamine oxidase inhibitors (MAOIs) tranylcypromine (TCP) and phenelzine (PLZ) are powerful antidepressants that come with an equally powerful stigma, and are thus rarely prescribed-despite their well-established effectiveness. Some of these preconceptions appear to stem from unclarity, as the etiology of a rare but important side effect, 'spontaneous hypertension' (SH)-a significant increase in blood pressure absent dietary tyramine ingestion-remains improperly elucidated. This paper aims at uprooting some of the stigma surrounding MAOIs by advancing the trace amine (TA) theory as the causative underpinning of SH. This theory posits that SH results from the considerable influx of TAs observed following TCP-or PLZ-administration. TAs are known, albeit at greatly supraphysiological levels, to raise blood pressure on account of their propensity to exert potent indirect sympathomimetic effects; additionally, some research posits that TAs may induce vasoconstrictive effects partly or wholly separate therefrom, which would then constitute a second hypertensive mechanism. TAs are endogenous to the human body in low quantities. Both TCP and PLZ cause marked elevations of 2-phenylethylamine (PEA), meta-and para-tyramine (m-/p-TYR), octopamine (OA), and tryptamine (TRYP), following both acute and (sub) chronic administration. This paper holds that TYR plays a pivotal role in causing SH, due to its strong pressor effect. Cautious treatment of SH is advised, given its typically self-limiting nature. The risk of hypotensive overshoots must be taken into account. For severe cases, this paper urges reconsideration, following suitable confirmation trials, of antipsychotics (notably risperidone) as these agents may reduce striatal p-TYR levels.

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Effects of tranylcypromine on the concentrations of some trace amines in the diencephalon and hippocampus of the rat

Cited by 20 publications

References 17 publications

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

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

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The trace amine theory of spontaneous hypertension as induced by classic monoamine oxidase inhibitors

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