Beta-Aminopropylbenzene
Beta-Aminopropylbenzene Uses, Dosage, Side Effects, Food Interaction and all others data.
Beta-Aminopropylbenzene, 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. Beta-Aminopropylbenzene, 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. Beta-Aminopropylbenzene 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.
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.
| Trade Name | Beta-Aminopropylbenzene |
| Availability | Prescription only |
| Generic | Amphetamine |
| Amphetamine Other Names | alpha-Methylbenzeneethaneamine, Amfetamina, Amfetamine, Amfetaminum, Amphetamine, beta-Aminopropylbenzene, beta-Phenylisopropylamin, Desoxynorephedrine, rac-amphetamine |
| Related Drugs | Adderall, Vyvanse, methylphenidate, phentermine, Concerta, Strattera, modafinil, Ritalin, semaglutide, dextroamphetamine |
| Type | |
| Formula | C9H13N |
| Weight | Average: 135.2062 Monoisotopic: 135.104799421 |
| Protein binding | The reported protein binding of amphetamine is relatively low and register to be of 20%. |
| Groups | Approved, Illicit, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Beta-Aminopropylbenzene is a CNS stimulant and sympathomimetic agent indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).
Beta-Aminopropylbenzene 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.
Beta-Aminopropylbenzene is also being used nowadays off-label for the treatment of obesity, depression and chronic pain.
Beta-Aminopropylbenzene is also used to associated treatment for these conditions: Attention Deficit Hyperactivity Disorder (ADHD), BMI >30 kg/m2, Depression, Narcolepsy, Pain, Chronic
How Beta-Aminopropylbenzene works
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. Beta-Aminopropylbenzene, 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.
Toxicity
The mean lethal serum concentration is reported to be of 6.4 mg/l. Acute amphetamine overdose can lead to hyperthermia, respiratory depression, seizures, metabolic acidosis, renal failure, hepatic injury, and coma. Some of the neurologic effects have been shown to be agitation, aggressive behavior, irritability, headache, and hallucinations. In the cardiovascular site, there have been reports of arrhythmia, cardiomyopathy, myocardial infarction or ischemic stroke. Lastly, in the GI tract, there are reports if abdominal pain, vomiting, diarrhea, cramps, anorexia and GI hemorrhage. A dose of 1-2 g of amphetamine is known to cause severe intoxication but some chronic abusers can report usage of even 5-15 g per day.
In animal studies, there is no evidence of carcinogenic potential, not clastogenic or to affect fertility or early embryonic development.
Food Interaction
- Take with or without food.
[Moderate] GENERALLY AVOID: Alcohol may potentiate the cardiovascular effects of amphetamines.
The exact mechanism of interaction is unknown.
In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state. The interaction was suspected in a case report of a 20-year-old male who experienced retrosternal chest pain shortly after drinking alcohol and taking a double dose of his amphetamine The patient had no family history of cardiovascular diseases, and his past medical history was remarkable only for ADHD. Prior to the episode, the patient had not taken his medication for weeks and had been drinking whiskey the previous three nights before going to bed. The patient was diagnosed with myocardial infarction likely secondary to amphetamine-induced coronary vasospasm.
MANAGEMENT: Concomitant use of amphetamines and alcohol should be avoided if possible, especially in patients with a history of heart disease.
Beta-Aminopropylbenzene Hypertension interaction
[Major] The use of CNS stimulants is contraindicated in patients with significant cardiovascular impairment such as uncompensated heart failure, severe coronary disease, severe hypertension (including that associated with hyperthyroidism or pheochromocytoma), cardiac structural abnormalities, serious arrhythmias, etc.
Sudden death has been reported in adults and children taking CNS stimulant treatment.
Additionally, stroke, myocardial infarction, chest pain, syncope, arrhythmias and other symptoms have been reported in adults under treatment.
A careful assessment of the cardiovascular status should be done in patients being considered for treatment.
This includes family history, physical exam and further cardiac evaluation (EKG and echocardiogram).
Patients who develop symptoms should have a detailed cardiac evaluation and if needed, treatment should be suspended.
Hypertension interaction[Major] CNS stimulant medications have shown to increase blood pressure, and their use might be contraindicated in patients with severe hypertension.
Caution should be used when administering to patients with preexisting high blood pressure and other cardiovascular conditions.
All patients under treatment should be regularly monitored for changes in blood pressure and heart rate.
Beta-Aminopropylbenzene Drug Interaction
Major: duloxetine, escitalopram, fluoxetine, bupropionModerate: albuterol, levothyroxine, ascorbic acidUnknown: aripiprazole, amphetamine / dextroamphetamine, amphetamine / dextroamphetamine, zolpidem, diphenhydramine, omega-3 polyunsaturated fatty acids, lamotrigine, pregabalin, quetiapine, cyanocobalamin, cholecalciferol, lisdexamfetamine, alprazolam
Beta-Aminopropylbenzene Disease Interaction
Major: cardiovascular, glaucoma, agitation, cardiac disease, glaucoma, hypertension, liver disease, psychiatric disorders, substance abuse, ticsModerate: bipolar disorders, psychotic disorders, renal dysfunction, seizure disorders, diabetics
Volume of Distribution
Beta-Aminopropylbenzene is reported to have a high volume of distribution of 4 L/kg.
Elimination Route
Beta-Aminopropylbenzene is well absorbed in the gut and as it is a weak base hence the more basic the environment the more of the drug is found in a lipid-soluble form and the absorption through lipid-rich cell membranes is highly favored. The peak response of amphetamine occurs 1-3 hours after oral administration and approximately 15 minutes after injection and it presents a bioavailability of over 75%. Complete amphetamine absorption is usually done after 4-6 hours.
Half Life
The half-life of amphetamine highly depends on the isomer. For d-amphetamine, the reported half-life is of approximately 9-11 hours while for l-amphetamine the half-life is reported to be of 11-14 hours. The urine pH can modify this pharmacokinetic parameter which can vary from 7 hours in acid urine to 34 hours for alkaline urine.
Clearance
The reported normal clearance rate is of 0.7 L.h/kg. This clearance has been shown to get significantly reduced in patients with renal impairment reaching a value of 0.4 L.h/kg.
Elimination Route
The elimination of amphetamine is mainly via the urine from which about 40% of the excreted dose is found as unchanged amphetamine. About 90% of the administered amphetamine is eliminated 3 days after oral administration. The rate of elimination of amphetamine highly depends on the urine pH in which acidic pH will produce a higher excretion of amphetamine and basic pH produces a lower excretion.
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