Inhibition of fatty acid amide hydrolase by URB597 attenuates the anxiolytic-like effect of acetaminophen in the mouse elevated plus-maze test.

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Zaitone SA, El-Wakeil AF, Abou-El-Ela SH

Inhibition of fatty acid amide hydrolase by URB597 attenuates the anxiolytic-like effect of acetaminophen in the mouse elevated plus-maze test.

Behav Pharmacol. 2012 Aug;23(4):417-25. doi: 10.1097/FBP.0b013e3283566065.

PubMed ID

22750843 [ View in PubMed

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Abstract

Acetaminophen is the most widely used analgesic/antipyretic drug. It is metabolized into N-arachidonoylphenolamine (AM404), which inhibits the reuptake of anandamide. In view of the role of endocannabinoids in the effect of acetaminophen, we tested its anxiolytic-like effect by observing the behavior of mice using the elevated plus-maze test. The results indicated that acetaminophen [100 and 200 mg/kg, intraperitoneally (i.p.)] exerted an anxiolytic-like effect that was represented by higher percentage open-arm time, percentage open-arm entries, and total number of head dips compared with the vehicle control (P<0.05). Inhibition of fatty acid amide hydrolase, an enzyme involved in the cerebral metabolism of acetaminophen into AM404, using URB597 (0.07 mg/kg, i.p.), attenuated the anxiolytic-like effect of acetaminophen. Pretreatment with the cannabinoid type-1 receptor antagonist rimonabant (1 mg/kg, i.p.) antagonized the effect of acetaminophen. Remarkably, the selected doses of rimonabant or URB597 did not themselves induce any anxiolytic-like effect. Furthermore, the selected doses of acetaminophen (25, 50, 100, and 200 mg/kg, i.p.) did not significantly alter the locomotor activity of mice in the open-field test. In conclusion, these findings confirmed that acetaminophen shows an anxiolytic-like effect in mice that involves, at least in part, AM404-mediated accumulation of anandamide in the brain and consequent activation of cannabinoid type-1 receptors.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Acetaminophen	Fatty-acid amide hydrolase 1	Protein	Humans	Unknown	Substrate	Details