NAPQI

NAPQI

Identifiers
IUPAC name N-(4-Oxo-1-cyclohexa-2,5-dienylidene)acetamide
Synonyms	N-Acetyl-p-benzoquinone imine; N-Acetylimidoquinone
CAS Number	50700-49-7 N
PubChem CID	39763
IUPHAR/BPS	6299
ChemSpider	36356 Y
UNII	G6S9BN13TI
ChEBI	CHEBI:29132 Y
ChEMBL	CHEMBL33232 Y
ECHA InfoCard	100.168.312
Chemical and physical data
Formula	C8H7NO2
Molar mass	149.147 g/mol
3D model (Jmol)	Interactive image
SMILES O=C\1/C=C\C(=N/C(=O)C)/C=C/1
InChI InChI=1S/C8H7NO2/c1-6(10)9-7-2-4-8(11)5-3-7/h2-5H,1H3 Y Key:URNSECGXFRDEDC-UHFFFAOYSA-N Y
NY (what is this?)

NAPQI (N-acetyl-p-benzoquinone imine) is a toxic byproduct produced during the xenobiotic metabolism of the analgesic paracetamol (acetaminophen). It is normally produced only in small amounts, and then almost immediately detoxified in the liver.

However, under some conditions in which NAPQI is not effectively detoxified (usually in case of paracetamol overdose), it causes severe damage to the liver. This becomes apparent 3–4 days after ingestion and may result in death from fulminant liver failure several days after the overdose.

In adults, the primary metabolic pathway for paracetamol is glucuronidation. This yields a relatively non-toxic metabolite, which is excreted into bile and passed out of the body. A small amount of the drug is metabolized via the pathway (to be specific, CYP3A4 and CYP2E1) into NAPQI, which is extremely toxic to liver tissue, as well as being a strong biochemical oxidizer. In an average adult, only a small amount (approximately 10% of a therapeutic paracetamol dose) of NAPQI is produced, which is inactivated by conjugation with glutathione. The amount of NAPQI produced differs in certain populations.

The minimum dosage at which paracetamol causes toxicity usually is 7.5 to 10g in the average person. The lethal dose is usually between 10 g and 15 g. Concurrent alcohol intake lowers these thresholds significantly. Chronic alcoholics may be more susceptible to adverse effects due to reduced glutathione levels. Other populations may experience effects at lower or higher dosages depending on differences in P-450 enzyme activity and other factors which affect the amount of NAPQI produced. In general, however, the primary concern is accidental or intentional paracetamol overdose. Since the drug is available over the counter in most jurisdictions, it is a common choice for suicide attempts.

When a toxic dose of paracetamol is ingested, the normal glucuronide pathway is saturated and large amounts of NAPQI are produced. Liver reserves of glutathione are depleted by conjugation with this excess NAPQI. The mechanism by which toxicity results is complex, but is believed to involve reaction between unconjugated NAPQI and critical proteins as well as increased susceptibility to oxidative stress caused by the depletion of glutathione.