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Vol. 282, Issue 1, 243-247, 1997
Department of Pharmacology and Toxicology, Medical College of
Virginia, Virginia Commonwealth University, Richmond, Virginia
The endogenous cannabinoid anandamide (AN) has been reported to produce
pharmacological effects similar to those of
9-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 µCi
3H-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 of
3H. Also, samples from brain, adrenal gland and plasma were
extracted with ethyl acetate and analyzed by HPLC to separate
3H-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.
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