Substituted β-hydroxyamphetamine
Substituted β-hydroxyamphetamines, or simply β-hydroxyamphetamines, also known as phenylisopropanolamines, phenylpropanolamines, norephedrines, or cathinols, are derivatives of β-hydroxyamphetamine with one or more chemical substituents. They are substituted phenethylamines, phenylethanolamines, and amphetamines, and are closely related to but distinct from the substituted cathinones. Examples of β-hydroxyamphetamines include the β-hydroxyamphetamine stereoisomers phenylpropanolamine and cathine and the stereospecific N-methylated β-hydroxyamphetamine derivatives ephedrine and pseudoephedrine, among many others.
In terms of pharmacological activity, the β-hydroxyamphetamines include indirectly acting norepinephrine and dopamine releasing agents and directly acting α- and β-adrenergic receptor agonists, among other actions. In contrast to their amphetamine counterparts, ephedrine and 4-fluoroephedrine are not agonists of the human trace amine-associated receptor 1. With regard to medical and other uses, β-hydroxyamphetamines are employed as sympathomimetics, decongestants, bronchodilators, vasoconstrictors, vasodilators, tocolytics, antitussives, cardiac stimulants, antihypotensive agents, appetite suppressants, psychostimulants, wakefulness-promoting agents, antidepressants, euphoriants or recreational drugs, and performance-enhancing drugs, among others.
β-Hydroxyamphetamines have increased hydrophilicity and lower lipophilicity relative to their amphetamine counterparts owing to their β-hydroxyl group. For comparison, the predicted log P of amphetamine is 1.8, of β-hydroxyamphetamine is 0.8, and of cathinone is 1.1. As a result of their reduced lipophilicity, they are generally less able to cross the blood–brain barrier and show greater peripheral selectivity in comparison to the corresponding amphetamine analogues. This makes the β-hydroxyamphetamines less applicable for use as centrally-acting agents but more applicable for peripherally-specific uses such as sympathomimetic stimulation. Besides different physicochemical properties, there is also a large drop in the potency of β-hydroxyamphetamines as monoamine releasing agents in vitro relative to amphetamines and cathinones.
List of substituted β-hydroxyamphetamines
| Generic or Trivial Name | Chemical Name | # of Subs |
| β-Hydroxyamphetamine | β-Hydroxy-α-methylphenethylamine | 0 |
| Phenylpropanolamine | β-Hydroxyamphetamine, - | 0 |
| -Phenylpropanolamine | β-Hydroxyamphetamine, - | 0 |
| -Phenylpropanolamine | β-Hydroxyamphetamine, - | 0 |
| Norpseudoephedrine | β-Hydroxyamphetamine, - | 0 |
| Cathine | β-Hydroxyamphetamine, - | 0 |
| L-Norpseudoephedrine | β-Hydroxyamphetamine, - | 0 |
| β-Hydroxy-N-methylamphetamine | β-Hydroxy-N-methylamphetamine | 1 |
| Racephedrine | β-Hydroxy-N-methylamphetamine, - | 1 |
| Ephedrine | β-Hydroxy-N-methylamphetamine, - | 1 |
| -Ephedrine | β-Hydroxy-N-methylamphetamine, - | 1 |
| Racemic pseudoephedrine | β-Hydroxy-N-methylamphetamine, - | 1 |
| Pseudoephedrine | β-Hydroxy-N-methylamphetamine, - | 1 |
| -Pseudoephedrine | β-Hydroxy-N-methylamphetamine, - | 1 |
| meta-Hydroxynorephedrine | 3,β-Dihydroxyamphetamine | 1 |
| Metaraminol | 3,β-Dihydroxyamphetamine, - | 1 |
| para-Hydroxynorephedrine | 4,β-Dihydroxyamphetamine | 1 |
| Oxyfedrine | β-Hydroxy-N-'-amphetamine, - | 1 |
| Alifedrine | β-Hydroxy-N-'-amphetamine, - | 1 |
| Tinofedrine | β-Hydroxy-N-amphetamine, - | 1 |
| Cafedrine | β-Hydroxy-N-amphetamine | 1 |
| Methylephedrine | β-Hydroxy-N,''N-dimethylamphetamine, - | 2 |
| N''-Methylpseudoephedrine | β-Hydroxy-N,''N-dimethylamphetamine, - | 2 |
| Cinnamedrine | β-Hydroxy-N''-methyl-N-cinnamylamphetamine | 2 |
| Etafedrine | β-Hydroxy-N-methyl-N-ethylamphetamine, - | 2 |
| 4-Fluoroephedrine | 4-Fluoro-β-hydroxy-N-methylamphetamine | 2 |
| Oxilofrine | 4,β-Dihydroxy-N-methylamphetamine | 2 |
| Corbadrine | 3,4,β-Trihydroxyamphetamine | 2 |
| Methoxamine | 2,6-Dimethoxy-β-hydroxyamphetamine | 2 |
| Hexapradol | α-Desmethyl-α-hexyl-β-hydroxy-β-phenylamphetamine | 2 |
| Erythrohydrobupropion | 3-Chloro-β-hydroxy-N-''tert-butylamphetamine, erythro- | 2 |
| Threohydrobupropion | 3-Chloro-β-hydroxy-N''-tert-butylamphetamine, threo- | 2 |
| Ritodrine | 4,β-Dihydroxy-N-amphetamine | 2 |
| Isoxsuprine | 4,β-Dihydroxy-N-'-amphetamine | 2 |
| Suloctidil | 4-Isopropylthio-β-hydroxy-N-octylamphetamine | 2 |
| Buphenine | 4,β-Dihydroxy-N-'-amphetamine | 2 |
| Trecadrine | β-Hydroxy-N-methyl-N-'-amphetamine | 2 |
| Ethylnorepinephrine | β,3,4-Trihydroxy-α-desmethyl-α-ethylamphetamine | 3 |
| Dioxifedrine | 3,4,β-Trihydroxy-N-methylamphetamine | 3 |
| Dioxethedrin | 3,4,β-Trihydroxy-N-ethylamphetamine | 3 |
| Butaxamine | 3,6-Dimethoxy-β-hydroxy-N-''tert-butylamphetamine, - | 3 |
| Isoetarine | 3,4,β-Trihydroxy-α-desmethyl-α-ethyl-N''-isopropylamphetamine | 4 |
| Procaterol | 2,3-'-4,β-dihydroxy-N-isopropyl-α-desmethyl-α-ethyl- amphetamine, - | 5 |