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Naproxen

C14H14O3 organic

Properties

StateSolid (white to off-white crystalline powder)
ColorWhite to off-white
SolubilityPractically insoluble in water (15.9 mg/L at 25°C); soluble in ethanol and DMSO
Melting Point155-156°C
Boiling PointDecomposes before boiling

About Naproxen

Naproxen (C14H14O3, 230.259 g/mol) is the propionic-acid NSAID that anchors the over-the-counter pain category in the US under the brand name Aleve, and it is one of the earliest examples of a pharmaceutical sold as a single enantiomer. Syntex synthesized and patented the drug in 1976 with a then-novel asymmetric route that delivered the pure (S)-(+) form, exploiting the fact that the (R) enantiomer is essentially inactive against COX-1 and COX-2 and was associated with hepatotoxicity in early animal studies. Mechanistically, naproxen is a non-selective cyclooxygenase inhibitor — it blocks both isoforms with comparable potency, suppressing prostaglandin synthesis from arachidonic acid and thereby reducing inflammation, fever, and pain transmission. The defining clinical advantage versus ibuprofen is the half-life: 12 to 17 hours in plasma, which permits 12-hour dosing intervals (typically 220 mg q12h OTC, 500 mg q12h prescription) instead of the every-4-to-6-hour regimen ibuprofen requires. The longer exposure does come with trade-offs — chronic naproxen use carries the same NSAID-class GI ulceration and renal risks as other non-selective COX inhibitors. The cardiovascular profile is the bright spot: large meta-analyses have consistently placed naproxen at the lower end of NSAID CV risk, possibly because sustained COX-1 inhibition mimics low-dose aspirin's anti-platelet effect.

Where you'll encounter it

If you've ever taken Aleve for a sprained ankle or a tension headache, you've taken 220 mg of naproxen sodium — the salt form because it dissolves and absorbs faster than the free acid. Pharmacy techs see naproxen in two main contexts: the OTC blue-and-white tablets and the prescription 500 mg generics that rheumatologists hand out for osteoarthritis flares. In the medicinal chemistry lab, the compound is one of the standard teaching examples for chiral resolution because the historical Syntex route, the modern asymmetric hydrogenation, and the lipase-mediated kinetic resolution all give different ee values that students can compare by chiral HPLC. Anyone who has worked emergency medicine has also seen the downside — long-term naproxen users showing up with melena from a NSAID-induced gastric bleed, particularly elderly patients on it for chronic arthritis pain.

Common Uses

  • Over-the-counter analgesic for headache, dental pain, and menstrual cramps
  • Prescription anti-inflammatory for osteoarthritis and rheumatoid arthritis flares
  • Acute gout treatment at 750 mg loading then 250 mg q8h until resolved
  • Antipyretic for adult fever (preferred over aspirin in dengue-endemic regions)
  • Tendinitis and bursitis pain management in sports medicine clinics
  • Teaching example for asymmetric synthesis and chiral HPLC resolution
  • Reference standard for non-selective COX-1/COX-2 inhibition in pharmacology assays

Safety Information

GHS Health Hazard classification (chronic toxicity). Common adverse effects: dyspepsia (10-20% of users), nausea, headache, mild fluid retention. Serious risks with chronic use: GI ulceration and bleeding (NNH around 100 over 6 months), renal impairment from sustained prostaglandin suppression, and elevated blood pressure. Contraindicated in active GI bleed, severe renal impairment (CrCl < 30 mL/min), late-pregnancy (third-trimester premature ductus closure), and within 14 days of CABG surgery. The FDA boxed warning covers cardiovascular thrombotic events and GI bleeding for the entire NSAID class, though naproxen sits at the lower CV-risk end. Do not co-administer with other NSAIDs. Standard adult OTC dose: 220 mg q8-12h, max 660 mg/day; prescription max 1000-1500 mg/day.

This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals.

Constituent Elements

Frequently Asked Questions

What is the molar mass of naproxen?
Naproxen (C14H14O3) is 230.259 g/mol: 14 C × 12.011 + 14 H × 1.008 + 3 O × 15.999. The commercial OTC form is naproxen sodium (252.245 g/mol), which has slightly faster onset because the carboxylate dissolves and absorbs more rapidly from the stomach than the protonated free acid does. A 220 mg naproxen sodium tablet contains about 200 mg of naproxen base.
How is naproxen different from ibuprofen?
Both are propionic-acid NSAIDs that non-selectively inhibit COX-1 and COX-2, but the kinetics differ sharply. Ibuprofen has a 2-4 hour plasma half-life and needs dosing every 4-6 hours; naproxen has a 12-17 hour half-life and works with twice-daily dosing. Large CV meta-analyses (the 2013 CNT collaboration in particular) place naproxen at lower cardiovascular risk than ibuprofen or diclofenac. The trade-off: GI bleeding risk is comparable or slightly higher for naproxen because the longer exposure means more sustained COX-1 inhibition in the gastric mucosa.
Why does chirality matter for naproxen?
Only the (S)-(+) enantiomer is active as a COX inhibitor — the (R) form is essentially inert at the target and was hepatotoxic in early Syntex animal studies. That hepatotoxicity is what pushed the company to develop a stereoselective synthesis in the 1970s, making naproxen one of the first chiral pharmaceuticals marketed as a single enantiomer rather than a racemate. The case is now the standard teaching example for why chirality matters in drug design, alongside thalidomide, and it directly motivated the FDA's 1992 policy statement requiring sponsors to characterize both enantiomers of any new chiral drug.