Pseudoephedrine
(1S,2S)-2-(methylamino)-1-phenylpropan-1-ol
Overview
Pseudoephedrine belongs to Stimulants.
Effects
- As a decongestant it clears nasal and sinus congestion. Users often notice mild alertness or a slight stimulant 'lift' from the noradrenaline release.
- Common or higher-dose effects include insomnia, restlessness, nervousness, palpitations, raised heart rate and blood pressure, and occasionally headache or difficulty passing urine.
- It is a much milder central stimulant than ephedrine or amphetamine and has low intrinsic abuse potential. Its main illicit significance is as a methamphetamine precursor.
Dosing & duration
Oral (tablets, capsules or liquid, immediate- and extended-release formulations).. Pseudoephedrine is an over-the-counter decongestant, not a recreational drug. It is only a weak stimulant. The figures below are standard therapeutic doses. Cardiovascular effects (raised heart rate and blood pressure) and insomnia increase at higher doses. It should be avoided in uncontrolled hypertension or heart disease and never combined with MAO inhibitors. Note that pseudoephedrine is a controlled methamphetamine precursor, so retail sales are quantity-limited and kept behind the pharmacy counter.
Dose ranges
60 mg every 4–6 h
120 mg every 12 h, or 240 mg once daily
240 mg/day
Duration
≈30 minutes
Immediate-release ≈4–6 h, extended-release up to 12–24 h
Possible insomnia or restlessness
Chemical & Physical Properties
| Formula | C10H15NO |
| Molar mass | 165.23 g/mol |
| State | Solid (crystalline) |
| Melting point | 118–120 °C |
| Boiling point | Not reported |
| Density | Not reported |
| Vapor pressure | Not reported |
| pKa | 10.3 (0 °C, amine) |
| LogP | 0.89 |
| Solubility | Sparingly soluble in water. Freely soluble in alcohol or ether, Very soluble in benzene |
| Refractive index | Not reported |
Identifiers & Synonyms
| CAS | 90-82-4 |
| CAS (enantiomer) | |
| PubChem CID | 7028 |
| InChIKey | KWGRBVOPPLSCSI-WCBMZHEXSA-N |
| InChI | InChI=1S/C10H15NO/c1-8(11-2)10(12)9-6-4-3-5-7-9/h3-8,10-12H,1-2H3/t8-,10+/m0/s1 |
| SMILES | CN[C@@H](C)[C@@H](O)c1ccccc1 |
Synonyms
- Sudafed
- (+)-pseudoephedrine
- (1S,2S)-(+)-pseudoephedrine
Pharmacodynamics & Biochemistry
Pseudoephedrine is a sympathomimetic amine and the (1S,2S)-(+)-diastereomer of ephedrine, used mainly as an oral nasal decongestant (Sudafed): it constricts the dilated blood vessels of the swollen nasal mucosa through α-adrenergic stimulation, relieving congestion. Like ephedrine it is a mixed-acting sympathomimetic, but predominantly INDIRECT. A comprehensive transporter/receptorome screen found that ephedrine-type compounds act mainly as substrates of the noradrenaline transporter (NET), promoting noradrenaline release, with only weak α2-adrenergic and 5-HT7 binding (Ki 1–10 µM) and no significant β- or α1-adrenergic activity. Pseudoephedrine is a weak releaser: its noradrenaline-release potency (EC50 ≈224 nM) is roughly 4–5× lower than ephedrine's (≈43–72 nM), with even weaker dopamine release and negligible serotonin release: consistent with its milder central-stimulant effect (values below). Because its direct receptor affinities are weak, its decongestant and adverse effects: vasoconstriction, and at higher doses raised heart rate and blood pressure, insomnia and restlessness: are driven largely by the noradrenaline it releases rather than by direct receptor agonism. Pseudoephedrine is eliminated largely unchanged in the urine, and its half-life is strongly pH-dependent, acidic urine shortens it markedly, so urinary pH influences both its duration and its effect.
Biological targets
- NET
- Adrenergic system
Binding & functional measurements
| Target | Measurement | Species |
|---|---|---|
| Norepinephrine transporter | pEC50 6.65 | Rat (brain synaptosomes) |
| Dopamine transporter | pEC50 5.7 | Rat (brain synaptosomes) |
Pharmacokinetics
| Bioavailability | Oral, well absorbed (high oral bioavailability) |
| Tmax | ≈1–3 h |
| Half-life | ≈5–8 h (markedly shorter in acidic urine) |
| Vd | Not reported |
| Protein binding | Not reported |
| Metabolism | Limited hepatic metabolism |
| Excretion | Largely renal, excreted unchanged (pH-dependent) |
Toxicology & Safety
Not reported
Pseudoephedrine can cause insomnia, restlessness, palpitations, raised blood pressure and headache. It must not be used with MAO inhibitors. European safety measures advise against use in severe or uncontrolled hypertension or severe acute or chronic kidney disease or renal failure because of the risk of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS). Stop taking it and seek urgent medical assistance for sudden severe headache, vomiting, confusion, seizures or visual changes. Retail restrictions also apply because it can be diverted as a methamphetamine precursor.[3][2][5][7]
Legal Status
US: OTC: behind the counter (restricted). UK: Pharmacy medicine (P). DE: Pharmacy only
Interactions & Contraindications
Drug interactions
Contraindications
No interactions or contraindications listed.
Usage & Context
- A standard over-the-counter oral decongestant (Sudafed and many combination cold/flu products) for nasal and sinus congestion, and for Eustachian-tube/ear congestion.
- Its main non-medical significance is as a methamphetamine precursor, which is why its sale is restricted and monitored worldwide. Direct recreational use is limited by its weak stimulant effect.
Sources & Evidence
- PubChem: Pseudoephedrine (CID 7028) — identifiers & experimental properties
- Rothman RB, Vu N, Partilla JS, et al. (2003). In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates. J Pharmacol Exp Ther 307:138-45.
PMID 12954796 · doi:10.1124/jpet.103.053975
- FDA / DailyMed: Pseudoephedrine prescribing information — pharmacokinetics & metabolism
- IUPHAR/BPS Guide to PHARMACOLOGY: pseudoephedrine (ligand 7286) — identifier record (no quantitative target-activity data listed) CC BY-SA 4.0
- DEA Diversion Control: Combat Methamphetamine Epidemic Act — pseudoephedrine as a List I precursor chemical
- Wikipedia: Pseudoephedrine (medical use, pharmacology & legal status) CC BY-SA 4.0
- EMA: pseudoephedrine measures to minimise PRES and RCVS risk (2024)