A variety of prodrugs of amphetamine and/or methamphetamine exist, and include amfecloral, amfetaminil, benzphetamine, clobenzorex, D-deprenyl, deprenyl, dimethylamphetamine, ethylamphetamine, fencamine, fenethylline, fenproporex, furfenorex, lisdexamfetamine, mefenorex, prenylamine, and selegiline.

[6] A number of synthetic Russian amphetamine derivatives have been developed, including alafen (amphetamine–β-alanine), feprosidnine, gamofen (amphetamine–GABA), mesocarb, methylphenatine, pabofen (amphetamine–PABA), phenatine (amphetamine–niacin; N-nicotinoylamphetamine), phenylphenamine (phenylamphetamine), propylphenamine (propylamphetamine), pyridoxiphen (amphetamine–pyridoxine), and thiophenatine (N-thionicotinoylamphetamine).

Typical reaction is substitution by methyl and sometimes ethyl groups at the amine and phenyl sites:[8][9][10] Ephedra was used 5000 years ago in China as a medicinal plant; its active ingredients are alkaloids ephedrine, pseudoephedrine, norephedrine (phenylpropanolamine) and norpseudoephedrine (cathine).

Over-the-counter use of substituted amphetamines was initiated in the early 1930s by the pharmaceutical company Smith, Kline & French (now part of GlaxoSmithKline), as a medicine (Benzedrine) for colds and nasal congestion.

Subsequently, amphetamine was used in the treatment of narcolepsy, obesity, hay fever, orthostatic hypotension, epilepsy, Parkinson's disease, alcoholism and migraine.

[15] During World War II, amphetamines were used by the German military to keep their tank crews awake for long periods, and treat depression.

[20] Ongoing trials are investigating its efficacy as an adjunct to psychotherapy in the management of treatment-resistant post-traumatic stress disorder (PTSD).