Phenylpropanolamine (PPA), sold under many brand names, is a sympathomimetic agent used as a decongestant and appetite suppressant.

[4][12] Side effects of phenylpropanolamine include increased heart rate and blood pressure.

[11][16][13] PPA acts as a norepinephrine releasing agent, indirectly activating adrenergic receptors.

[17][18][19][10] It was once thought to act as a sympathomimetic with additional direct agonist action on adrenergic receptors, but this proved wrong.

[13][14] It has also been used to suppress appetite and promote weight loss in the treatment of obesity and has shown effectiveness for this indication.

[29] The Journal of Clinical Neuroscience reported the case of an otherwise healthy male who started experiencing intense and recurrent sensations of déjà vu upon taking the drugs amantadine and phenylpropanolamine together to relieve flu symptoms.

[30] He found the experience so interesting that he completed the full course of his treatment and reported it to the psychologists to write up as a case study.

[21] It is about 100 to 200 times less potent than epinephrine (adrenaline) or norepinephrine (noradrenaline) in its sympathomimetic effects, although responses are variable depending on tissue.

[6] The hydroxyl group of phenylpropanolamine at the β carbon increases its hydrophilicity, reduces its permeation through the blood–brain barrier, and limits its central nervous system (CNS) effects.

[21][6][5] Phenylpropanolamine is more lipophilic than structurally related sympathomimetics with hydroxyl groups on the phenyl ring like epinephrine (adrenaline) and phenylephrine and has greater brain permeability than these agents.

[4][5][6] The methyl group at the α carbon of phenylpropanolamine blocks metabolism by monoamine oxidases (MAOs).

[14] The hydroxyl group at the β carbon of phenylpropanolamine also helps to increase metabolic stability.

[4] Conversely, there is likely to be accumulation of phenylpropanolamine with renal impairment due to its dependence on urinary excretion.

[20] Phenylpropanolamine, structurally, is in the substituted phenethylamine class, consisting of a cyclic benzene or phenyl group, a two carbon ethyl moiety, and a terminal nitrogen, hence the name phen-ethyl-amine.

Exogenous compounds in this family are degraded too rapidly by monoamine oxidase to be active at all but the highest doses.

[51] In general, N-methylation of primary amines increases their potency, whereas β-hydroxylation decreases CNS activity, but conveys more selectivity for adrenergic receptors.

[53] For comparison to phenylpropanolamine, the experimental log P of methamphetamine is 2.1,[54] of amphetamine is 1.8,[55][54] of ephedrine is 1.1,[56] of pseudoephedrine is 0.7,[57] of phenylephrine is -0.3,[58] and of norepinephrine is -1.2.

[23][11] In the United States, phenylpropanolamine is no longer sold due to an increased risk of haemorrhagic stroke.

[9][1][2] Brand names of phenylpropanolamine include Acutrim, Appedrine, Capton Diet, Control, Dexatrim, Emagrin Plus A.P., Glifentol, Kontexin, Merex, Monydrin, Mydriatine, Prolamine, Propadrine, Propagest, Recatol, Rinexin, Tinaroc, and Westrim, among many others.

In the United Kingdom, phenylpropanolamine was available in many "all in one" cough and cold medications which usually also feature paracetamol (also known as acetaminophen) or another analgesic and caffeine and could also be purchased on its own.

It is no longer approved for human use, however, and a European Category 1 Licence is required to purchase or acquire phenylpropanolamine for academic or research use.

In this advisory, the FDA requested but did not require that all drug companies discontinue marketing products containing phenylpropanolamine.

[71] Under the 2020 CARES Act, it requires FDA approval before it can be marketed again effectively banning the drug, even as a prescription.

[72] Because of its potential use in amphetamine manufacture, phenylpropanolamine is controlled by the Combat Methamphetamine Epidemic Act of 2005.

[74] On 13 September 2011, Madras High Court revoked a ban on the manufacture and sale of pediatric drugs phenylpropanolamine and nimesulide.

[78] Phenylpropanolamine hydrochloride chewable tablets contain the same active ingredient (phenylpropanolamine hydrochloride) in the same concentration and dosage form as the approved brand name drug product, Proin chewable tablets, which were first approved in August 2011.