Repositioning Candidate Details
| Candidate ID: | R0068 |
| Source ID: | DB00182 |
| Source Type: | approved; illicit; investigational |
| Compound Type: | small molecule |
| Compound Name: | Amphetamine |
| Synonyms: | (+-)-alpha-Methylphenylethylamine; 1-phenyl-2-aminopropane; alpha-Methylbenzeneethaneamine; Amfetamine; Amphetamine; beta-Aminopropylbenzene; Desoxynorephedrine; rac-(2R)-1-phenylpropan-2-amine; rac-amphetamine; α-methylbenzeneethaneamine; α-methylphenethylamine; β-aminopropylbenzene; β-phenylisopropylamine |
| Molecular Formula: | C9H13N |
| SMILES: | CC(N)CC1=CC=CC=C1 |
| Structure: |
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| DrugBank Description: | Amphetamine, a compound discovered over 100 years ago, is one of the more restricted controlled drugs. It was previously used for a large variety of conditions and this changed until this point where its use is highly restricted. Amphetamine, with the chemical formula alpha-methylphenethylamine, was discovered in 1910 and first synthesized by 1927. After being proven to reduce drug-induced anesthesia and produce arousal and insomnia, amphetamine racemic mix was registered by Smith, Kline and French in 1935. Amphetamine structure presents one chiral center and it exists in the form of dextro- and levo-isomers. The first product of Smith, Kline and French was approved by the FDA on 1976. During World War II, amphetamine was used to promote wakefulness in the soldiers. This use derived into a large overproduction of amphetamine and all the surplus after the war finalized ended up in the black market, producing the initiation of the illicit abuse. |
| CAS Number: | 300-62-9 |
| Molecular Weight: | 135.2062 |
| DrugBank Indication: | Amphetamine is indicated for the treatment of attention-deficit/hyperactivity disorders (ADHD) as well as for the treatment of central nervous system disorders such as narcolepsy. ADHD is a complex disorder associated with the substantial heterogeneity in etiology, clinical presentation, and treatment outcome. ADHD comes from a complex interplay between interdependent genetic and non-genetic factors which cause complex mental disorders in children and teenagers. On the other hand, narcolepsy is a chronic sleep disorder typically resenting during adolescence and characterized by excessive daytime sleepiness. Amphetamine is also being used nowadays off-label for the treatment of obesity, depression and chronic pain. |
| DrugBank Pharmacology: | From its mechanism of action, it has been demonstrated that amphetamine augments the concentration of noradrenaline in the prefrontal cortex and dopamine in the striatum on a dose and time-dependent manner. The indistinct release of neurotransmitters which include adrenaline is known to produce cardiovascular side effects. There are old reports of a cognitive enhancement related to the administration of amphetamine in which improvements in intelligence test scores were reported. In ADHD, amphetamine has been largely showed to produce remarkable improvements in school performance, behavior, and demeanor. The effect was shown to be produced through both racemic forms and to this date, the use of racemic forms 3:1 (D:L) is very common. The therapeutic effect of amphetamine on serotonin does not seem to have a significant clinical effect on ADHD as observed on comparative studies with amphetamine and fenfluramine, a powerful serotonin releasing factor. However, the indirect effect on serotonin might have an effect on the depression and anxiety profile of ADHD. Studies regarding the illicit use of amphetamine in which heavy consumers were studied proved the generation of a paranoid state which flagged this drug as a psychiatric danger compound. This observation was supported by the continuous reports of misuse in patients under depression. |
| DrugBank MoA: | It is important to consider that amphetamine has a very similar structure to the catecholamine neurotransmitters mainly on the presence of a long planar conformation, the presence of an aromatic ring and nitrogen in the aryl side chain. Amphetamine, as well as other catecholamines, is taken into presynaptic nerve terminals by the association with two sodium ions and one chloride ion. The complex of the amphetamine with the ions is actively transported by monoamine reuptake transporters. As amphetamine acts competitively with the endogenous monoamines, the greater the number of amphetamines the more internalized amphetamine will be found. Once inside the presynaptic terminal, amphetamine displaces other monoamines to be stored by VMAT2 which produces the pumping of the neurotransmitters into the synapse by a process called retro-transport. This process of release of neurotransmitters is approximately fourfold more potent in the d-isomer for the release of dopamine. The mechanism of action of amphetamine is complemented by the inhibition of the reuptake and of monoamine oxidase which acts synergistically to produce a significant increase the monoamine concentration. This activity is not done as an inhibitor per se but more as a competitive substrate and thus, amphetamine is known to be a weak dopamine reuptake inhibitor, moderate noradrenaline reuptake inhibitor and very weak serotonin reuptake inhibitor. From this specific action, the l-isomer is known to be significantly less potent. Lastly, amphetamine is known to be an inhibitor of the mitochondrial-bound enzyme MAO which is the catalytic enzyme in charge of degrading all the excess of neurotransmitters. This mechanism of action is often overpassed as amphetamine is a weak MAO inhibitor but this mechanism cannot be dismissed. |
| Targets: | Synaptic vesicular amine transporter inhibitor; Sodium-dependent dopamine transporter negative modulator; Cocaine- and amphetamine-regulated transcript protein agonist; Trace amine-associated receptor 1 agonist; Sodium-dependent noradrenaline transporter agonist&substrate; Alpha adrenergic receptor agonist; Beta adrenergic receptor agonist; Dopamine D2 receptor binder; Amine oxidase [flavin-containing] B inhibitor; Sodium-dependent serotonin transporter binder; Monoamine oxidase inhibitor; vesicular monoamine transporter 2 (VMAT2) |
| Inclusion Criteria: | Indication associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I17 | 1596 | Mental depression | Mental depression | disease of mental health/ cognitive disorder/ mood disorder | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |