Drug Report: Amphetamine

The chemical compound known as amphetamine belongs to a class of drugs called

psychostimulants. These drugs induce temporary changes in an individual’s mental state.

Typically, psychostimulants drugs help to increase one’s alertness or act as antidepressants to

bring about a positive mood swing. In regards to amphetamine, its primary function is to

improve focus and attentiveness. Amphetamine based drugs, such as Adderall and Dexedrine,

are often prescribed to treat individuals suffering from attention deficit hyperactivity disorder

(ADHD) and narcolepsy. Another drug, Benzedrine, uses a racemic mixture of amphetamines to

stimulate the dilation of nasal and bronchial tubes to help treat people with asthma. However,

Benzedrine can also induce a strong euphoric effect and was one of the first amphetamine

based drugs to be misused for recreational purposes. Methamphetamine (or N-

methylamphetamine) is another, more dangerous, example of an amphetamine that is misused

for recreation. In large doses, this drug induces a powerful euphoric effect triggered by a

massive release of dopamine in the brain. Methamphetamine is a very powerful amphetamine

stimulant because it readily dissolves in nonpolar solvents and can easily pass through the

blood brain barrier; a fluid structure that restricts the flow of large hydrophilic molecules but

allows small hydrophobic molecules to enter. In general, most amphetamine drugs use their

hydrophobic properties to easily diffuse through the blood brain barrier. Once inside the brain,

amphetamines will interact with molecules involved with neuron signaling to increase the

concentration of dopamine being transmitted between neural synapses. It is thought that

amphetamines bind to dopamine transporting molecules and alter their structure in a way that

keeps them activated, thus prolonging the transmission of dopamine throughout the brain.

Brent Tollerud

Sythesis of Amphetamine:

“Amphetamine can be synthesized by the sequential alkylation of methyl acetoacetate

with dimethyl sulfate and benzyl chloride, followed by hydrolysis and deacetylation to give

2-phenylpropionic acid, which through reaction with thionyl chloride and ammonia forms,

2-phenylpropionamide. Upon treatment with aqueous sodium hypochlorite, this amide

undergoes Hofmann rearrangement to form racemic amphetamine (phenyl-2-aminopropane).

The order in which methyl acetoacetate is alkylated with dimethyl sulfate and benzyl

chloride is of utmost importance to produce the desired dialkylacetoacetate isomer. If methyl

acetoacetate is benzylated before it is methylated, the methyl group adds to the benzylic

carbon instead of on the acetoacetate alpha-carbon. By first methylating the sodium salt

of methyl acetoacetate and then benzylate the sodium salt of the formed alpha-methyl-

acetetoacetic ester, the formation of the desired isomer is ensured ("Drugs-forum," 2008.)”

Sources:

- Bluebelly. (2012). Retrieved from http://www.bluebelly.org.au/howtheywork/articlebabb.html?

aid=156&cid=28

- Drugs-forum (2008). Retrieved from http://www.drugs-forum.com/forum/showthread.php?t=126

-Medlineplus. (2010, Jan. 08). Retrieved from http://www.nlm.nih.gov/medlineplus/druginfo/meds/

a601234.html

-National Institute of Drug Abuse. (2010). Retrieved from National Institute of Drug Abuse website:

http://www.drugabuse.gov/publications/infofacts/methamphetamine

- Smith, S. E. (07 N). Wisegeek. Retrieved from http://www.wisegeek.com/what-is-benzedrine.htm