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OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

The Biodisposition and Metabolism of Anandamide in Mice

Karen A. Willoughby, Sandra F. Moore, Billy R. Martin and Earl F. Ellis
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 243-247;
Karen A. Willoughby
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Sandra F. Moore
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Billy R. Martin
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Earl F. Ellis
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Abstract

The endogenous cannabinoid anandamide (AN) has been reported to produce pharmacological effects similar to those of Δ9-tetrahydrocannabinol but with a shorter duration of action. Also, AN is known to be metabolized to arachidonic acid. The purpose of this study was to examine the time course of distribution and metabolism of AN. Male mice were each administered 20 μCi3H-AN and 50 mg/kg AN (i.v.). At 1, 5, 15 and 30 min after administration, the animals were sacrificed, and various tissues were removed, solubilized and counted to determine the distribution of3H. Also, samples from brain, adrenal gland and plasma were extracted with ethyl acetate and analyzed by HPLC to separate3H-labeled AN, arachidonic acid and other metabolites. AN was detectable in brain by 1 min after injection. At 1 min after injection, the rank order of radioactivity per milligram or microliter of tissue was adrenal > lung > kidney > plasma > heart > liver > diaphragm > brain > fat. Although the 1 and 5 min metabolic profiles of brain 3H showed that AN was clearly present, most AN had already been transformed to arachidonic acid and other polar metabolites, and there were almost no detectable brain levels of AN at 15 and 30 min. In plasma and adrenal gland, AN was the predominant form at 1 and 5 min. Our experiments confirm that AN quickly reaches the brain and suggest that rapid metabolism of AN plays a key role in the time course of the pharmacological activity of this naturally occurring cannabinoid receptor ligand.

Footnotes

  • Send reprint requests to: Dr. Earl F. Ellis, Box 980613, MCV Station, Richmond, VA 23298-0613.

  • ↵1 Supported by National Institute of Health Grant DA-08677 and a Center of Excellence Grant-in-Aid from the Commonwealth of Virginia.

  • Received June 31, 1996.

  • Abbreviations:
    AN
    anandamide
    AA
    arachidonic acid
    PMSF
    phenylmethyl-sulfonyl fluoride
    Δ9-THC
    Δ9-tetrahydrocannabinol
    • Accepted March 10, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
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OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

The Biodisposition and Metabolism of Anandamide in Mice

Karen A. Willoughby, Sandra F. Moore, Billy R. Martin and Earl F. Ellis
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 243-247;

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OtherPROSTAGLANDINS, LEUKOTRIENES AND OTHER EICOSANOIDS

The Biodisposition and Metabolism of Anandamide in Mice

Karen A. Willoughby, Sandra F. Moore, Billy R. Martin and Earl F. Ellis
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 243-247;
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