Elevated circulating levels of anandamide after administration of the transport inhibitor, AM404

Andrea Giuffrida, Fernando Rodriguez De Fonseca, Felice Nava, Patrick Loubet-Lescoulié, Daniele Piomelli

Research output: Contribution to journalArticlepeer-review

114 Scopus citations

Abstract

The biological actions of the endogenous cannabinoid anandamide are terminated by carrier-mediated transport into neurons and astrocytes, followed by enzymatic hydrolysis. Anandamide transport is inhibited by the compound N-(4-hydroxyphenyl)arachidonylamide (AM404). AM404 potentiates several responses elicited by administration of exogenous anandamide, suggesting that it may also protect endogenous anandamide from inactivation. To test this hypothesis, we studied the effects of AM404 on the plasma levels of anandamide using high-performance liquid chromatography/mass spectrometry (HPLC/MS). Systemic administration of AM404 (10 mg kg-1 intraperitoneal, i.p.) caused a gradual increase of anandamide in rat plasma, which was significantly different from untreated controls at 60 and 120 min after drug injection. In plasma, both AM404 and anandamide were associated with a plasma protein, which we identified as albumin by non-denaturing polyacrylamide gel electrophoresis. AM404 (10 mg kg-1, i.p.) caused a time-dependent decrease of motor activity, which was reversed by the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide·hydrochloride (SR141716A, 0.5 mg kg-1, i.p). These results are consistent with the hypothesis that AM404 inhibits anandamide inactivation in vivo. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)161-168
Number of pages8
JournalEuropean Journal of Pharmacology
Volume408
Issue number2
DOIs
StatePublished - Nov 17 2000

Keywords

  • Anandamide
  • Anandamide transport
  • Cannabinoid
  • Fatty acid ethanolamides
  • High-performance liquid chromatography
  • Mass spectrometry

ASJC Scopus subject areas

  • Pharmacology

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