Amphetamine Amphetamine

Group Members:

Kwong Ka Yi

Mak Cheuk Kin

Lead Compound DiscoveryLead Compound Discovery

First synthesized in 1887 By Lazar Edelearnu But have no pharmacological use

Resynthesized in 1927 By Gordon Alles Used as a decongestant

Molecular modificationMolecular modification

Ephedrine (2-methylamino-1-phenylpropan-1-ol)

Amphetamine (1-phenylpropan-2-amine)

Ephedrine

Amphetamine

Formulation DevelopmentFormulation Development

Psychostimulant Increased wakefulness Decreased fatigue

Examples of popular brands Containing amphetamine as active ingredient

Adderall Vyvanse Dexedrine

AdderallAdderall

Developed by Shire Pharmaceutical in 1996 Available in 2 formulations:

Immediate release Extended release Formulations modified

Strong effect on absorption & excretion of the racemic DL-amphetamine

Increased reabsorption

dangerously high amphetamine serum level

At molecular levelAt molecular level

A mixture of amphetamine salts Racemic amphetamine aspartate monohydrate Dextroamphetamine saccharide Detroamphtetamine sulphate Racemic amphetamine sulphate

Active ingredients Dextroamphetamine

Racemic DL-amphetamine

VyvanseVyvanse

Developed by New River Pharmaceutical in 2005

Available formulations Pills of several dosages Formulation modified

Single-enantiomer amphetamine

Reduce side effect

At molecular levelAt molecular level

Active ingredients: Lisdexamphetamine Dextroamphetamine

Amphetamine dextroamphetamine

lisdexamphetamine

Dissociate ions Covalent amide bond hydrolysis

Lisdexamphetamine

Dextroamphetamine

Dexedrine Dexedrine

Formulations available Tablet Sustained-release capsules Formulation modified

Exhibit better preventive effect on the neurotransmitters

more obvious fatigue reduction

At molecular levelAt molecular level

Amphetamine Dextroamphetamine

Dextroamphetamine

= enantiomer of amphetamine

Safety tests & Human Trials

Adderall Adderall

Test Duration : 2 years Treatment : ADHD Result :

Adderall XR – better tolerability Significant long-term ADHD sympton control

Vyvanse

Test Duration : 1 year Treatment : ADHD Result :

Fairly good tolerability Side effects frequently reported

Decreased appetite Headache Decreased weight Insomnia

Dexedrine

Treatment : ADHD Narcolepsy Depression Psychiatric syndrome

Dexedrine

Result : Improve attention span & behaviour Reduce fatigue in some patients

Approval for Marketing

Adderall

Potential addictive property Powerful ability to raise blood pressure Approved for the treatment of ADHD ONLY

Vyvanse

Date Approval

23th February 2007 U.S. Food and Drug Administration (FDA)

3rd January 2008 U.S. Food and Drug Administration (FDA)

19th February 2009 Health Canada

Dexedrine

ADHD Narcolepsy

Depression Weight Loss