[11][12] Pharmaceuticals that contain levoamphetamine are currently indicated and prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), obesity, and narcolepsy in some countries.
[10][15] While pharmaceutical formulations containing enantiopure levoamphetamine are no longer manufactured,[10] levomethamphetamine (levmetamfetamine) is still marketed and sold over-the-counter as a nasal decongestant.
[17][7] Levoamphetamine has been used in the treatment of attention deficit hyperactivity disorder (ADHD) both alone and in combination with dextroamphetamine at different ratios.
[10][12] The clinical dosages and potencies of levoamphetamine and dextroamphetamine in the treatment of ADHD have been fairly similar in these older studies.
[2][3] Because of the greater central nervous system effect of the dextrorotatory enantiomer (i.e., dextroamphetamine), sold as Dexedrine, prescription of the Benzedrine brand fell and was eventually discontinued.
[6] Levoamphetamine, similarly to dextroamphetamine, acts as a reuptake inhibitor and releasing agent of norepinephrine and dopamine in vitro.
[10] Levoamphetamine and dextroamphetamine are both also relatively weak reversible inhibitors of monoamine oxidase (MAO) and hence can inhibit catecholamine metabolism.
[35] In rodent studies, both dextroamphetamine and levoamphetamine dose-dependently induce the release of dopamine in the striatum and norepinephrine in the prefrontal cortex.
[10] As with rodent studies, levoamphetamine and dextroamphetamine have been found to be similarly potent in elevating norepinephrine levels in cerebrospinal fluid in monkeys.
[10] Although dextroamphetamine is more potent than levoamphetamine, both enantiomers can maximally increase striatal dopamine release by more than 5,000% of baseline.
[10] Dextroamphetamine has greater potency in producing stimulant-like effects in rodents and non-human primates than levoamphetamine.
[10][7][44] Potency ratios of dextroamphetamine versus levoamphetamine with single doses of 5 to 80 mg in terms of psychological effects in humans including stimulation, wakefulness, activation, euphoria, reduction of hyperactivity, and exacerbation of psychosis have ranged from 1:1 to 4:1 in a variety of older clinical studies.
[46][47][48][49] These findings parallel the clinical results in which both levoamphetamine and dextroamphetamine have been found to be effective in the treatment of ADHD in humans.
[10][12] Unlike the case of dextroamphetamine versus dextromethamphetamine, in which the latter is more effective than the former, levoamphetamine is substantially more potent as a dopamine releaser and stimulant than levomethamphetamine.
[5][58] The peak levels of levoamphetamine are proportionally similar to those of dextroamphetamine with administration of amphetamine at varying ratios.
[5] Food does not affect the peak levels or overall exposure to levoamphetamine or dextroamphetamine with IR racemic amphetamine.
Racemic amphetamine contains two optical isomers in equal amounts, dextroamphetamine (the dextrorotatory enantiomer) and levoamphetamine.
[61][62] Ephedrine ((1R,2S)-β-hydroxy-N-methylamphetamine), an analogue and derivative of amphetamine and the major pharmacologically active constituent of ephedra, was first isolated from the plant in 1885.
[63][60] Another plant, known as Catha edulis (khat), also naturally contains amphetamines, specifically cathine ((1S,2S)-β-hydroxyamphetamine) and cathinone (β-ketoamphetamine).
[10] This led to the discovery of the stimulating effects of amphetamine in humans in 1929 after Alles injected himself with 50 mg of the drug.
[10] Dextroamphetamine was found to be the more potent of the two enantiomers of amphetamine and was introduced as an enantiopure drug under the brand name Dexedrine in 1937.
[10] Levoamphetamine was studied in the treatment of attention deficit hyperactivity disorder (ADHD) in the 1970s and was found to be clinically effective for this condition similarly to dextroamphetamine.
[10] As a result of this study, use of racemic amphetamine in the treatment of ADHD dramatically declined in favor of dextroamphetamine.
[67][68][69][70] Due to their lower efficacy in stimulating dopamine release and their reduced potency as psychostimulants, levoamphetamine and levomethamphetamine would theoretically be expected to have less misuse potential than the corresponding dextroamphetamine and dextromethamphetamine forms.
[92][94][95][96] Other selective MAO-B inhibitors that do not metabolize into amphetamine metabolites or have associated cardiovascular effects, such as rasagiline, have also been developed and introduced.