Propylhexedrine, sold under the brand name Benzedrex among others, is a nasal decongestant of the alkylamine family and related to the arylalkylamines.

[2] Propylhexedrine was first used medically in 1949, with the release of Benzedrex by Smith, Kline & French, and it has been used, mainly within the United States, since then.

[3] Propylhexedrine is used to treat acute nasal congestion related to the common cold, allergies, and hay fever.

[11] When used as an inhaler, the most common adverse effects warned about for propylhexedrine are temporary discomfort (e.g., stinging or burning sensations) or rebound congestion.

[12] However, the use of propylhexedrine products in manners not intended by their labeling can result in severe adverse effects not typically encountered in therapeutic settings.

[12] Public health agencies such as the Food and Drug Administration (FDA) have advised propylhexedrine products only be used in the manners directed on their label.

[13] As noted by the FDA, the most common symptoms of propylhexedrine overdose are the following: "[r]apid heart rate, agitation, high blood pressure, chest pain, tremor, hallucinations, delusions, confusion, nausea, and vomiting.

Propylhexedrine works mainly as an adrenergic agonist, when used at therapeutic doses in an inhaler dosage form.

[22] At higher doses, propylhexedrine affects the central nervous system as a norepinephrine–dopamine releasing agent (NDRA).

[23] Propylhexedrine likely exerts such effects in a manner similar to related alkylamines such as cyclopentamine, methylhexanamine, and tuaminoheptane.

[27] Propylhexedrine undergoes metabolism via N-demethylation, C-oxidation, N-oxidation, dehydrogenation, and hydrolysis to form various metabolites such as norpropylhexedrine, cyclohexylacetoxime, cyclohexylacetone, and 4-hydroxypropylhexedrine.

Many of the salts of propylhexedrine are stable, clear to off-white crystalline substances that readily dissolve in water.

Propylhexedrine can be synthesized from cyclohexylacetone through the reductive amination of an intermediary imine over an aluminum-mercury amalgam in the presence of a hydrogen source.

[33] Due to its structure, administration of propylhexedrine can lead to false positives for phenethylamine derivatives on urinalysis panels.

[35] Propylhexedrine's medical use as a decongestant evolved from desires to find safer alternatives to previous agents.

[41] The manufacture of propylhexedrine products for therapeutic use is typically performed based on guidelines established in government regulations and pharmacopeia monographs.

[42][5] The illicit manufacture or diversion of propylhexedrine by clandestine chemists for use as a recreational drug has been documented in academic literature.

[50] Propylhexedrine was used recreationally during a brief period in the 1970s after increased government regulation on earlier decongestants due to misuse.

Furthermore, pursuant to DEA regulations, certain Benzedrex inhalers are specifically exempt from the Controlled Substances Act.

[62] Multiple public health agencies (most notably within the United States) have warned against the recreational use of propylhexedrine and advised for its use only as directed by a product's labeling; nonetheless it has been reported, through the literature as early as 1959, that propylhexedrine products have been used for recreational purposes.

[23] In 2021, the Food and Drug Administration (FDA) issued the following warning[13] in regard to recreational use of propylhexedrine products in manners inconsistent with their labeling: ...[T]he abuse and misuse of the over-the-counter (OTC) nasal decongestant propylhexedrine can lead to serious harm such as heart and mental health problems.

Seek medical attention immediately for by calling [emergency services] or Poison Control...for anyone using propylhexedrine who experiences [the following.]

[These following reactions are] [s]evere anxiety or agitation, confusion, hallucinations, or paranoia[,] [r]apid heartbeat or abnormal heart rhythm[,] [or] [c]hest pain or tightness[.

The guidance states that recreational use of propylhexedrine is not permissible by service-members, can open its participants up to disciplinary action, and carries potentially fatal risks: When disciplining a member for suspected use of any drug, it is important to consult [legal counsel] on how to proceed, [according to the Office of Drug Demand Reduction]...This is especially important when the evidence supporting discipline consists of scientific reports and data that may require special assistance in their interpretation.