Propacetamol targets the same pathways as acetaminophen. Acetaminophen enters the central nervous system and acts centrally. It binds to cyclooxygenase (COX) and prevents the metabolism of arachidonic acid to prostaglandin. A reduction in prostaglandin formation relieves pain and reduces fever. The exact mechanism of action has yet to be fully elucidated.

In vitro, Propacetamol is hydrolyzed by plasma esterases into acetaminophen. Acetaminophen inhibits prostaglandin synthesis. Propacetamol reduces aspirin-induced elevation of malondialdehyde (MDA) in gastric mucosa and plasma, regulates the levels of gastric mucosal glutathione (GSH and GSSG) to maintain cellular antioxidant defense, and increases gastric mucosal uric acid (UA) levels.

In vivo, Propacetamol exerts antipyretic and analgesic effects after metabolism to acetaminophen. It provides a dose-dependent protective effect against gastric mucosal damage and can be used for studying gastric mucosal injury by interfering with oxidative stress. The water-soluble nature of propacetamol facilitates its formulation for intravenous use.

Propacetamol's conversion to acetaminophen by plasma esterases can be studied in vitro. Enzyme assays typically involve incubating propacetamol with plasma or purified esterases and measuring the formation of acetaminophen using HPLC or LC-MS. The compound's stability and hydrolysis kinetics can be characterized.

In vitro cell experiments with Propacetamol involve treating cells with the compound and assessing its effects on oxidative stress, glutathione levels, and prostaglandin synthesis. The compound's protective effects against gastric mucosal damage can be studied in gastric epithelial cells.

In vivo animal studies with Propacetamol have been conducted using rodent models to study its analgesic, antipyretic, and gastroprotective effects. The compound is typically administered via oral gavage or intravenous injection. Detailed protocols regarding dosage, treatment duration, and specific animal models are available in the literature.

Absorption, Distribution and Excretion
The bioavailability of 2 g of propatetamol is similar to that of 1 g of intravenously administered acetaminophen. Peak plasma concentrations are reached at the end of the infusion. Pharmacokinetic analysis of intravenously administered propatetamol showed significantly higher peak plasma concentrations than oral acetaminophen, and the time to peak concentration was also earlier. Cmax, Tmax, and AUC were 12.72 mcg/ml, 0.25 h, and 25.5 mcg·h/ml, respectively. Significant concentrations of acetaminophen were detected in the cerebrospinal fluid after propatetamol infusion. The metabolites of propatetamol are primarily excreted in the urine. Based on elimination rate, 90% of the administered dose is excreted within 24 hours primarily as glucuronide and sulfate conjugates. Less than 5% of the drug is excreted unchanged as acetaminophen. The volume of distribution of propatetamol is 1.29 L/kg.
The clearance rate of propatetamoxifen is 0.28 L/h/kg.
Metabolism/Metabolites
After administration, propatetamoxifen is completely converted to N,N-diethylglycine and acetaminophen by plasma esterases. The latter is the active metabolite. It has been reported that the active metabolite of propatetamoxifen can be converted to N-acetyl-p-benzoquinone imine via CYP2E1, which is a hepatotoxic metabolite.
Biological Half-Life
The half-life of propatetamoxifen is 3.6 hours.

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Propacetamol is rapidly hydrolyzed by plasma esterases to acetaminophen. Acetaminophen is metabolized in the liver via glucuronidation, sulfation, and oxidation pathways. The compound is water-soluble, which facilitates its formulation for intravenous use.

Protein Binding
Propapatemol is rapidly converted to acetaminophen, which often binds very weakly to plasma proteins.

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Propacetamol is considered safe for research use at typical concentrations. Acetaminophen has a well-established safety profile but can cause hepatotoxicity at high doses. As a prodrug, propacetamol is designed to improve the tolerability of acetaminophen. As a research compound, it is intended for laboratory use only.

Propacetamol is an α-amino acid ester. Propacetamol is a non-opioid analgesic with no major contraindications. It is a derivative of acetaminophen (paracetamol), with the molecular formula glycine-N,N-diethyl-4-(acetamino)phenyl ester. Propacetamol is an injectable form of acetaminophen, therefore it is a prodrug that can be completely hydrolyzed to acetaminophen. It is not yet marketed in the United States, but this prodrug has been widely used in France and other countries since 1985. Propacetamol is a water-soluble para-aminophenol derivative and an ester prodrug of acetaminophen, in which acetaminophen is conjugated with diethylglycine carboxylic acid, possessing analgesic and antipyretic effects. After intravenous injection, Propacetamol is hydrolyzed to the active form acetaminophen by plasma esterases. Although acetaminophen is widely used, its exact mechanism of action is not fully understood. This drug can enter the central nervous system and exert central effects. Acetaminophen binds to cyclooxygenase (COX), preventing the metabolism of arachidonic acid into prostaglandins. Reduced prostaglandin production can relieve pain and reduce fever. Acetaminophen may also exert its central effects by acting on cannabinoid receptors and N-methyl-D-aspartate (NMDA) receptors.

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Drug Indications
Propapatemotor is a prodrug of acetaminophen used intravenously to control fever and pain in perioperative multimodal analgesia.

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Mechanism of Action
As a prodrug, propapatemotor's mechanism of action is directly related to the activity of acetaminophen. The mechanism of action of acetaminophen is through the inhibition of prostaglandin synthesis. This inhibition is achieved by inhibiting COX-1 and COX-2 in an environment of low arachidonic acid and peroxide levels. The mechanism of action of acetaminophen is highly complex, involving the peripheral system (direct inhibition of COX), the central system (inhibition of COX, serotonergic descending neural pathways, the L-arginine/NO pathway, and the endocannabinoid system), and redox mechanisms. In the brain and spinal cord, acetaminophen can bind with arachidonic acid to form N-arachidonicylphenolamine. This metabolite is an activator of the capsaicin receptor (TRPV1) and the endocannabinoid receptor CB1.

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Propacetamol is an orally active prodrug of acetaminophen. It exerts antipyretic and analgesic effects after metabolism. It reduces aspirin-induced elevation of MDA and regulates gastric mucosal glutathione levels, providing a protective effect against gastric mucosal damage.

C14H20N2O3

264.3202

264.147

66532-85-2

Propacetamol hydrochloride;66532-86-3

68865

White to off-white solid powder

1.132 g/cm3

434.5ºC at 760 mmHg

216.6ºC

1.547

1.965

1

4

7

19

295

0

CCN(CC(OC1C=CC(NC(=O)C)=CC=1)=O)CC

QTGAJCQTLIRCFL-UHFFFAOYSA-N

InChI=1S/C14H20N2O3/c1-4-16(5-2)10-14(18)19-13-8-6-12(7-9-13)15-11(3)17/h6-9H,4-5,10H2,1-3H3,(H,15,17)

(4-acetamidophenyl) 2-(diethylamino)acetate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~100 mg/mL (~378.33 mM)
DMSO : ~33.33 mg/mL (~126.10 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.46 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (7.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (7.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 4: 100 mg/mL (378.33 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)