Effects of the analgesic acetaminophen (paracetamol) and its para-aminophenol metabolite on viability of mouse-cultured cortical neurons

Stephen Schultz, Mauris Desilva, Ting Ting Gu, Mei Qiang, Kyumin Whang

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Acetaminophen has been used as an analgesic for more than a hundred years, but its mechanism of action has remained elusive. Recently, it has been shown that acetaminophen produces analgesia by the activation of the brain endocannabinoid receptor CB1 through its para-aminophenol (p-aminophenol) metabolite. The objective of this study was to determine whether p-aminophenol could be toxic for in vitro developing mouse cortical neurons as a first step in establishing a link between acetaminophen use and neuronal apoptosis. We exposed developing mouse cortical neurons to various concentrations of drugs for 24hr in vitro. Acetaminophen itself was not toxic to developing mouse cortical neurons at therapeutic concentrations of 10-250μg/ml. However, concentrations of p-aminophenol from 1 to 100μg/ml produced significant (p<0.05) loss of mouse cortical neuron viability at 24hr compared to the controls. The naturally occurring endocannabinoid anandamide also caused similar 24-hr loss of cell viability in developing mouse cortical neurons at concentrations from 1 to 100μg/ml, which indicates the mechanism of cell death could be through the cannabinoid receptors. The results of our experiments have shown a detrimental effect of the acetaminophen metabolite p-aminophenol on in vitro developing cortical neuron viability which could act through CB1 receptors of the endocannabinoid system. These results could be especially important in recommending an analgesic for children or individuals with traumatic brain injury who have developing cortical neurons.

Original languageEnglish (US)
Pages (from-to)141-144
Number of pages4
JournalBasic and Clinical Pharmacology and Toxicology
Volume110
Issue number2
DOIs
StatePublished - Feb 2012

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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