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 (β-hydroxyphenethylamines), and amphetamines (α-methylphenethylamines), and are closely related to but distinct from the substituted cathinones (β-ketoamphetamines). 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 (TAAR1). 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 (in exercise and sports), 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 (XLogP3) 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

Side-chain-cyclized substituted β-hydroxyamphetamines

Some β-hydroxyamphetamines have had their side chain extended and cyclized. Examples include certain substituted phenylmorpholines like phenmetrazine and phendimetrazine and their analogues; substituted phenylmorpholines related to bupropion like radafaxine (cyclized (2S,3S)-hydroxybupropion) and manifaxine; certain substituted aminorexes like 4-methylaminorex and 4,4'-dimethylaminorex; and other compounds including cilobamine, diphenylprolinol, ifenprodil, levophacetoperane, pipradrol, rimiterol, traxoprodil, vibegron, and zilpaterol.

Activity profiles

See also

• Substituted amphetamine
• Substituted methylenedioxyphenethylamine
• Substituted cathinone
• Substituted phenylmorpholine
• 2Cs, DOx, 25-NB
• Substituted benzofurans
• List of aminorex analogues
• List of methylphenidate analogues
• Substituted tryptamine
• Substituted α-alkyltryptamines
• PiHKAL