Phenylpropanolamine

Phenylpropanolamine (PPA) is a sympathomimetic agent which is used as a decongestant and appetite suppressant. It is commonly used in prescription and over-the-counter cough and cold preparations. In veterinary medicine, it is used to control urinary incontinence in dogs. PPA is also known as β-hydroxyamphetamine, and is a member of the phenethylamine and amphetamine chemical classes. It is closely related to the cathinones (β-ketoamphetamines). The compound exists as four stereoisomers, which include d- and l-norephedrine and d- and l-norpseudoephedrine. d-Norpseudoephedrine is also known as cathine, and is found naturally in Catha edulis (khat). Pharmaceutical drug preparations of PPA have varied in their stereoisomer composition in different countries, which may explain differences in misuse and side effect profiles. Analogues of PPA include ephedrine, pseudoephedrine, amphetamine, methamphetamine, and cathinone. Although originally thought to act as a direct agonist of adrenergic receptors, PPA was subsequently found to show only weak or negligible affinity for these receptors, and has been instead characterized as an indirect sympathomimetic which acts by inducing norepinephrine release and thereby activating adrenergic receptors. It was patented in 1938. In the United States, PPA is no longer sold due to a purported increased risk of stroke in younger women. In a few countries in Europe, however, it is still available either by prescription or sometimes over-the-counter. In Canada, it was withdrawn from the market on 31 May 2001. It was voluntarily withdrawn from the Australian market by July 2001. In India human use of PPA and its formulations was banned on 10 February 2011, but the ban was overturned by the judiciary in September 2011. PPA acts primarily as a selective norepinephrine releasing agent. It also acts as a dopamine releasing agent with around 10-fold lower potency. The stereoisomers of the drug have only weak or negligible affinity for α- and β-adrenergic receptors. Many sympathetic hormones and neurotransmitters are based on the phenethylamine skeleton, and function generally in 'fight or flight' type responses, such as increasing heart rate, blood pressure, dilating the pupils, increased energy, drying of mucous membranes, increased sweating, and a significant number of additional effects. Norephedrine is a metabolite of amphetamine, as shown below. There are four optical isomers of PPA: dextro- and levo-norephedrine, and dextro- and levo-norpseudoephedrine. d-Norpseudoephedrine is also known as cathine, and occurs naturally in Catha edulis ('Khat').