Short- and Long-term Effects of P-ethynylphenylalanine on Brain Serotonin Levels
Overview
Affiliations
Changes in tissue and extracellular serotonin (5-HT) in raphe dorsalis, raphe medialis and in their main projections areas (hippocampus, striatum and frontal cortex) were investigated at short and long-term times after single injection (5 mg/kg ip) of a novel tryptophan hydroxylase inhibitor, p-ethynylphenylalanine (p-EPA). The 5-HT tissue concentration decreased significantly in raphe nuclei, 30 min post-injection and for 4 days, whereas it decreased from 24 hours post-injection in the 5-HT projections. Normal 5-HT levels reappeared after 12 days post-injection in all areas. Moreover, in the projection areas, the extracellular 5-HT levels decreased rapidly, 90, 40 and 30 min after p-EPA injection, in hippocampus, striatum and frontal cortex, respectively. Decreased accumulation of 5-hydroxytryptophan (5-HTP) under NSD-101 perfusion in the serotoninergic projections after p-EPA injection, confirmed the direct inhibitory effect of the drug on the tryptophan hydroxylase activity. These results demonstrated that p-EPA is a useful pharmacological tool which powerfully, acutely and irreversibly reduces the 5-HT levels.
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Maffei M Int J Mol Sci. 2020; 22(1).
PMID: 33375373 PMC: 7796270. DOI: 10.3390/ijms22010181.
Betari N, Sahlholm K, Morato X, Godoy-Marin H, Jauregui O, Teigen K Front Pharmacol. 2020; 11:593416.
PMID: 33324221 PMC: 7726444. DOI: 10.3389/fphar.2020.593416.
Phenylalanine Monitoring via Aptamer-Field-Effect Transistor Sensors.
Cheung K, Yang K, Nakatsuka N, Zhao C, Ye M, Jung M ACS Sens. 2019; 4(12):3308-3317.
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Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions.
Scotton W, Hill L, Williams A, Barnes N Int J Tryptophan Res. 2019; 12:1178646919873925.
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