Transporter-mediated actions of R-(-)-1-(benzofuran-2-yl)-2- propylaminopentane

Seiichiro Shimazu, Hiroko Tsunekawa, Fumio Yoneda, Hiroshi Katsuki, Akinori Akaike, Aaron Janowsky

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP] is a catecholaminergic and serotonergic activity enhancer that increases impulse-evoked catecholamine and serotonin release from nerve terminals, and is a candidate for symptomatic treatment of early Parkinson's disease. We now report the catecholamine and serotonin transporter-mediated actions of (-)-BPAP. The effects of (-)-BPAP on inhibition of neurotransmitter uptake and radioligand binding were assessed using human embryonic kidney 293 cells (HEK 293 cells) expressing cDNA for the human dopamine transporter (hDAT), norepinephrine transporter (hNET), and serotonin transporter (hSERT). The IC50 values for the effects of (-)-BPAP on [3H]dopamine, [3H]norepinephrine, and [3H]serotonin uptake were 42±9, 52±19, and 640±120 nM, respectively. The IC 50 values for the effects of (-)-BPAP on [125I]3β-(4- iodophenyl)tropane-2β-carboxylic acid methyl ester ([125I]RTI- 55) binding to hDAT, hNET, and hSERT were 16±2, 211±61, and 638±63 nM, respectively. The effects of (-)-BPAP on spontaneous and tyramine-induced norepinephrine and dopamine release from rat brain synaptosomes using a superfusion system were also assessed. Tyramine but not (-)-BPAP potentiated norepinephrine release. Furthermore, (-)-BPAP inhibited tyramine-induced norepinephrine release. Thus, (-)-BPAP may block tyramine-induced adverse effects such as hypertensive crisis. The actions of (-)-BPAP on the spontaneous and tyramine-induced dopamine release resembled its effects on norepinephrine release. We conclude that (-)-BPAP is not only catecholaminergic and serotonergic activity enhancer, but also a norepinephrine and dopamine uptake inhibitor and a weak serotonin uptake inhibitor that does not possess a tyramine-like action on catecholamine release, and is an inhibitor of tyramine-induced release of norepinephrine.

Original languageEnglish (US)
Pages (from-to)9-16
Number of pages8
JournalEuropean Journal of Pharmacology
Volume482
Issue number1-3
DOIs
StatePublished - Dec 15 2003

Fingerprint

Tyramine
Norepinephrine
Serotonin Plasma Membrane Transport Proteins
Norepinephrine Plasma Membrane Transport Proteins
Catecholamines
Dopamine
Dopamine Plasma Membrane Transport Proteins
Serotonin
Dopamine Uptake Inhibitors
Synaptosomes
Serotonin Uptake Inhibitors
1-(benzofuran-2-yl)-2-propylaminopentane
Inhibitory Concentration 50
Neurotransmitter Agents
Parkinson Disease
Complementary DNA
Kidney
Brain

Keywords

  • Catecholaminergic and serotonergic activity enhancer
  • Human embryonic kidney 293 cell
  • Parkinson's disease
  • R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane [(-)-BPAP]
  • Transporter
  • Tyramine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Transporter-mediated actions of R-(-)-1-(benzofuran-2-yl)-2- propylaminopentane. / Shimazu, Seiichiro; Tsunekawa, Hiroko; Yoneda, Fumio; Katsuki, Hiroshi; Akaike, Akinori; Janowsky, Aaron.

In: European Journal of Pharmacology, Vol. 482, No. 1-3, 15.12.2003, p. 9-16.

Research output: Contribution to journalArticle

Shimazu, Seiichiro ; Tsunekawa, Hiroko ; Yoneda, Fumio ; Katsuki, Hiroshi ; Akaike, Akinori ; Janowsky, Aaron. / Transporter-mediated actions of R-(-)-1-(benzofuran-2-yl)-2- propylaminopentane. In: European Journal of Pharmacology. 2003 ; Vol. 482, No. 1-3. pp. 9-16.
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