General
Preferred name
ACETAMINOPHEN
Synonyms
Acetaminophen mixture with butalbital ()
4'-Hydroxyacetanilide ()
4-Acetamidophenol ()
APAP ()
paracetamol ()
Apadaz-acetominophen ()
acetominophen ()
acetaminophen, Kowa ()
Disprol Jnr ()
Ofirmev ()
Neopap ()
Junior Parapaed ()
Disprol Paed ()
NSC-109028 ()
Calpol Six Plus ()
Parapaed Six Plus ()
Infadrops ()
Disprol Infant ()
Calpol ()
Medinol Under 6 ()
Abdine ()
Vermidon ()
Fennings ()
Datril ()
P-hydroxy-acetanilid ()
Panadol ActiFast Solb ()
Dafalgan ()
Paravict ()
Galpamol ()
Mandanol ()
Panaleve ()
Medinol ()
Calpol Six Plus Fastmelts ()
Rimadol ()
Cupanol ()
Tylenol ()
Placidex ()
Perfalgan ()
Medinol Over 6 ()
Panadol Advan ()
NSC-3991 ()
Phenaphen ()
Parapaed Jnr ()
Child Lemsip ()
Injectapap ()
Angiers ()
Medinol For Children ()
Alvedon ()
Hedex ()
Paldesic ()
Panadol Actifast ()
Panadol OA ()
Acephen ()
Doliprane ()
Panadol ()
Salzone ()
Tixymol ()
Disprol ()
Panadol Jnr ()
Tramil 500 ()
N-acetyl-p-aminophenol ()
Paracetamolum ()
Medised Plain ()
Miradol ()
Paramin ()
Biocetamol ()
Infants' Feverall ()
Panaleve 6 Plus ()
Efferalgan ()
Acetaminophen-d4 ()
Acetaminophen (CRM) ()
Acetaminophen-d4 (CRM) ()
P&D ID
PD002492
CAS
103-90-2
64315-36-2
60902-28-5
Tags
prodrug
natural product
drug
available
Approved by
PMDA
FDA
First approval
1968
Drug Status
approved
Drug indication
Antipyretic
Analgesic
Pain
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ROE
Acetaminophen metabolites are primarily excreted in the urine. Less than 5% is excreted in the urine as free (unconjugated) acetaminophen and at least 90% of the administered dose is excreted within 24 hours [F4124].
PHARMACODYNAMICS
Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic activity that is equal to that of acetylsalicylic acid. Acetaminophen lacks anti-inflammatory effects. Unlike the _salicylate_ drug class, acetaminophen does not interfere with tubular secretion of uric acid and does not affect acid-base balance if taken at the recommended doses. Acetaminophen does not interfere with hemostasis and does not have inhibitory activities platelet aggregation. Allergic reactions are rare occurrences following acetaminophen use [F4124].
INDICATION
For the treatment of mild to moderate pain and reduction of fever [F4124]. Acetaminophen _injection_ is indicated for [FDA label]: ⢠Management of mild to moderate pain ⢠Management of moderate to severe pain with adjunctive opioid analgesics ⢠Reduction of fever Due to its low potential to cause allergic reactions, this drug can be administered in patients who are intolerant to salicylates and those with an allergic diathesis, including bronchial asthmatics [F4124]. Specific dosing guidelines should be followed when administering acetaminophen to children [L5780].
ABSORPTION
Acetaminophen has 88% oral bioavailability and reaches peak plasma concentration 90 minutes after ingestion [A35815]. Peak blood levels of free acetaminophen are not reached until 3 hours after rectal administration of the suppository form of acetaminophen and the peak concentration in the blood is about 50% of that observed following an equivalent oral dose (10-20 mcg/mL) [F4124]. The percentage of a rectal dose of acetaminophen absorbed systemically is inconsistent, showed by wide variances in the bioavailability of acetaminophen following a rectal dose. Higher rectal doses or an increased frequency of administration may be used to attain blood concentrations of acetaminophen comparable to those attained after oral acetaminophen administration [FDA label].
HALF-LIFE
The half-life for adults is 2.5 h after an intravenous dose of 15 mg/kg [FDA label]. After an overdose, the half-life can range from 4 to 8 hours depending on the degree of injury to the liver, as it metabolizes acetaminophen [A35815]. More information on half-life for neonates and other populations may be found on the acetaminophen FDA label [FDA label].
PHARMACODYNAMICS
Animal and clinical studies have determined that acetaminophen has both antipyretic and analgesic effects. This drug has been shown to lack anti-inflammatory effects. As opposed to the _salicylate_ drug class, acetaminophen does not disrupt tubular secretion of uric acid and does not affect acid-base balance if taken at the recommended doses [F4124]. Acetaminophen does not disrupt hemostasis and does not have inhibitory activities against platelet aggregation [FDA label], [F4124]. Allergic reactions are rare occurrences following acetaminophen use [F4124].
INDICATION
In general, acetaminophen is used for the treatment of mild to moderate pain and reduction of fever [F4124]. It is available over the counter in various forms, the most common being oral forms.; ; Acetaminophen _injection_ is indicated for [FDA label]:; ; ⢠Management of mild to moderate pain; ; ⢠Management of moderate to severe pain with adjunctive opioid; analgesics; ; ⢠Reduction of fever; ; ; Because of its low risk of causing allergic reactions, this drug can be administered in patients who are intolerant to salicylates and those with allergic tendencies, including bronchial asthmatics [F4124]. Specific dosing guidelines should be followed when administering acetaminophen to children [L5780].
ROE
Acetaminophen metabolites are mainly excreted in the urine. Less than 5% is excreted in the urine as free (unconjugated) acetaminophen and at least 90% of the administered dose is excreted within 24 hours [F4124].
METABOLISM
Acetaminophen is the major metabolite of _phenacetin_ and _acetanilid_ [F4124]. Acetaminophen is mainly metabolized in the liver by first-order kinetics and its metabolism of comprised of 3 pathways: conjugation with glucuronide, conjugation with sulfate, and oxidation through the cytochrome P450 enzyme pathway, mainly CYP2E1, to produce a reactive metabolite (N-acetyl-p-benzoquinone imine or NAPQI). At normal therapeutic doses, NAPQI undergoes fast conjugation with glutathione and is subsequently metabolized to produce both cysteine and mercapturic acid conjugates [FDA label].; ; High doses of acetaminophen (overdoses) can lead to hepatic necrosis due to the depletion of glutathione and of binding of high levels of reactive metabolite (NAPQI) to important parts of liver cells. The abovementioned damage to the liver can be prevented by the early administration of sulfhydryl compounds, for example, methionine and N-acetylcysteine [A35814].
ABSORPTION
Acetaminophen has 88% oral bioavailability and reaches its highest plasma concentration 90 minutes after ingestion [A35815].; Peak blood levels of free acetaminophen are not reached until 3 hours after rectal administration of the suppository form of acetaminophen and the peak blood concentration is approximately 50% of the observed concentration after the ingestion of an equivalent oral dose (10-20 mcg/mL) [F4124].; ; The percentage of a systemically absorbed rectal dose of acetaminophen is inconsistent, demonstrated by major differences in the bioavailability of acetaminophen after a dose administered rectally. Higher rectal doses or an increased frequency of administration may be used to attain blood concentrations of acetaminophen similar to those attained after oral acetaminophen administration [FDA label].
HALF-LIFE
The half-life for adults is 2.5 h after an intravenous dose of 15 mg/kg [FDA label]. After an overdose, the half-life can range from 4 to 8 hours depending on the severity of injury to the liver, as it heavily metabolizes acetaminophen [A35815]. More information on half-life for neonates and other populations may be found on the acetaminophen FDA label [FDA label].
DESCRIPTION
Paracetamol is approved by the US FDA as acetaminophen. Paracetamol is a widely used analgesic and antipyretic drug.
(GtoPdb)
MOA
Although acetaminophen's exact mechanism of action has not been fully established, according to the [FDA label], it is categorized as an NSAID (a nonsteroidal anti-inflammatory drug) due to that fact that it inhibits the cyclooxygenase (COX) pathways [T518], and it is thought to exert central actions which lead to the improvement of pain symptoms [FDA label]. On theory is that acetaminophen increases the pain threshold by inhibiting two isoforms of cyclooxygenase, COX-1, COX-2, as well as COX-3 enzymes, which are involved in prostaglandin (PG) synthesis. Prostaglandins are responsible for pain sensations [A176366]. Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no peripheral anti-inflammatory effects. Though acetylsalicylic acid (aspirin) is an irreversible inhibitor of COX and directly blocks the active site of this enzyme, studies have shown that acetaminophen (paracetamol) blocks COX by an indirect mechanism [F4133]. This blockade has reduced efficacy when peroxides are present. This might explain why acetaminophen is effective in the central nervous system (CNS) and in endothelial cells but not in platelets and immune cells (which contain high peroxide levels). Studies also suggest that acetaminophen selectively blocks a variant form of the COX enzyme [A468] that is unique from the known variants COX-1 and COX-2. This enzyme has to been referred to as COX-3. Its exact mechanism of action is not fully understood at this time, but future research may promote further insight. The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centers in the brain, resulting in peripheral vasodilation, sweating, and dissipation of heat [F4133].
METABOLISM
Acetaminophen is the major metabolite of _phenacetin_ and _acetanilid_ [F4124]. Acetaminophen is mainly metabolized in the liver by first-order kinetics and its metabolism of comprised of 3 pathways: conjugation with glucuronide, conjugation with sulfate, and oxidation through the cytochrome P450 enzyme pathway, mainly CYP2E1, to produce a reactive intermediate metabolite (N-acetyl-p-benzoquinone imine or NAPQI). At normal therapeutic doses, NAPQI undergoes fast conjugation with glutathione and is subsequently metabolized to produce cysteine and mercapturic acid conjugates [FDA label]. High doses of paracetamol (overdoses) can lead to hepatic necrosis due to the depletion of glutathione and of binding of high levels of reactive metabolite (NAPQI) to vital cell components. The abovementioned damage to the liver can be prevented by the early administration of sulfhydryl compounds including methionine and N-acetylcysteine [A35814].
MOA
Although acetaminophen's exact mechanism of action has not been fully established, according to the FDA label [FDA label], it is categorized as an NSAID (a nonsteroidal anti-inflammatory drug) due to that fact that it inhibits the cyclooxygenase (COX) pathways [T518], and it is thought to exert central actions which ultimately lead to the alleviation of pain symptoms [FDA label]. ; ; One theory is that acetaminophen increases the pain threshold by inhibiting two isoforms of cyclooxygenase, COX-1 and COX-2, which are involved in prostaglandin (PG) synthesis. Prostaglandins are responsible for eliciting pain sensations [A176366]. Acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, therefore, has no peripheral anti-inflammatory effects. Though acetylsalicylic acid (aspirin) is an irreversible inhibitor of COX and directly blocks the active site of this enzyme, studies have shown that acetaminophen (paracetamol) blocks COX indirectly [F4133]. Studies also suggest that acetaminophen selectively blocks a variant type of the COX enzyme [A468] that is unique from the known variants COX-1 and COX-2. This enzyme has been referred to as _COX-3_. The antipyretic actions of acetaminophen are likely attributed to direct action on heat-regulating centers in the brain, resulting in peripheral vasodilation, sweating, and loss of body heat [F4133]. The exact mechanism of action of this drug is not fully understood at this time, but future research may contribute to deeper knowledge [F4133].
DESCRIPTION
Cyclooxygenase inhibitor; may be selective for COX-3
(Tocriscreen Plus)
DESCRIPTION
Cyclooxygenase inhibitor; may be selective for COX-3
(Tocriscreen Total)
DESCRIPTION
Cyclooxygenase inhibitor (COX-1 > COX-2)
(Tocris Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
1
Organisms
1
Compound Sets
32
AdooQ Bioactive Compound Library
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
MedChem Express Bioactive Compound Library
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
NURSA ligand set
Other bioactive compounds
Prestwick Chemical Library
ReFrame library
TargetMol Bioactive Compound Library
The Spectrum Collection
Tocris Bioactive Compound Library
Tocriscreen Plus
Tocriscreen Total
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
78
Molecular Weight
151.06
Hydrogen Bond Acceptors
2
Hydrogen Bond Donors
2
Rotatable Bonds
1
Ring Count
1
Aromatic Ring Count
1
cLogP
1.35
TPSA
49.33
Fraction CSP3
0.12
Chiral centers
0.0
Largest ring
6.0
QED
0.6
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Enzymes
Pathway
Immunology/Inflammation
Neuroscience
Anti-infection
Epigenetics
Metabolic Enzyme/Protease
Target
COX-1
COX-2
FAAH, PTGS1, PTGS2, TRPV1
Bacterial
COX
Endogenous Metabolite
Histone Acetyltransferase
Parasite
Primary Target
Cyclooxygenases
MOA
Inhibitor
Cyclooxygenase-3 Inhibitors
cyclooxygenase inhibitor
Member status
member
Indication
pain relief, fever
Disease Area
neurology/psychiatry, endocrinology
Therapeutic Indication
Analgesic
Therapeutic Class
CNS & PNS
Analgesics
Source data
