Phenethylamine and Amphetamine

Phenethylamine (phenyl-ethyl-amine): A phenyl ring, connected to an amine by an ethyl chain.

Phenethylamine is present in our nervous system, and is also the backbone of many psychoactive compounds including the neurotransmitters dopamine and norepinephrine and psychedelic compounds investigated by Shulgin in PiHKAL. It is sold as a nutritional supplement with stimulant effects as it acts as releaser of norepinephrine and dopamine in the brain, but is largely inactive due to extensive first-pass metabolism when taken orally ensuring very little passes the blood-brain barrier.

Amphetamine (alpha-methyl-phenethylamine): Phenethylamine methylated at the alpha carbon, the carbon closest to the functional amine group.

Amphetamine was first synthesized in 1887 by Lazăr Edeleanu as part of a series of compounds related to the herbal stimulant ephedrine. It rapidly increases the concentrations of dopamine, serotonin, and norepinephrine in the brain and has powerful motivating and euphoric effects. It has been used since its discovery to increase concentration and alertness, including World War II where British troops alone used 72 million amphetamine pills and today where Adderall is prescribed to children and adults diagnosed with ADHD.

Why is the line representing the methyl group wiggly instead of straight like you may be used to? Well, there are two possible stereoisomers of amphetamine that can be visualized more easily in 3D.

We can think of these as right and left handed versions - while they look identical at a glance, if we investigate their structure we cannot make them line up with each other no matter how much we rotate them around. We can think of the wiggly line as a methyl group coming out of, or going into, the page depending on the stereoisomer.

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    • patterned
    • November 24th, 2010

    Does the chirality of that methyl group have any affect on pharmacological action?

    I still don’t understand how they are formed or if there are ways to target a certain stereoisomer during synthesis. Maybe in the future you could go a little deeper into this?

    • Hey patterned,

      Definitely planning an article on this in the future - there’s some interesting differences in action with the stereoisomers of MDMA in isolation and conjunction.

      As for amphetamine, there are definitely differences. In general dextroamphetamine has more of an effect on the central nervous system, while levoamphetamine tends to affect the peripheral nervous system. This is not the whole story, as there are distinct behavioural effects noted as well, see Levoamphetamine and Dextroamphetamine: Differential Effect on Aggression and Hyperkinesis in Children and Dogs.

      Dextroamphetamine is sold as Dexedrine, while Adderall is a 50/50 mixture of dextroamphetamine and racemic amphetamine (resulting in a 75 dextro / 25 levo mix).

      In order to target a specific stereoisomer during synthesis, a chiral precursor must be used rather than the cheaper alternative of a racemic precusor.

        • patterned
        • November 24th, 2010

        Wow, great stuff. Levomethamphetamine suddenly makes sense..
        I’m looking forward to the MDMA stereoisomers article.

        If I could shamefully request another topic that I cannot seem to get a firm grasp on, it would be MAOIs and their interactions with the substituted PEAs.

    • patterned
    • November 24th, 2010

    Also, at the mention of phenethylamine, my girl brought home something called zi-ja (without the hyphens; I don’t want to link to it and give this crap any precedence in any search engine’s algorithm/indexing). She is an RN at a regional hospital and says this stuff is RAMPANT in the nursing world. It’s a pyramid scheme, naturally.
    She was given some free samples so I checked the ingredients and sure enough phenethylamine was present.

    I tried one of the pills the next day and was left with some mild stomach irritation which subsided into a chatty but somewhat uncomfortable headspace.
    Maybe I should start a psychedelic pyramid scheme… that would just be picking low hanging fruit though. That and the moral implications.

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