[saved316]

Lisdexamfetamine ((2S)-2,6-diamino-N-[(2S)-1-phenylpropan-2-yl]hexanamide) is a prodrug of the psychostimulant d-amphetamine coupled with the essential amino acid L-lysine. It was developed so that the amphetamine psychostimulant is released and activated more slowly as the prodrug molecule is hydrolyzed consequently cleaving off the amino acid-during the first pass through the intestines and/or the liver. Amphetamines target the trace amine-associated receptor 1 (TAAR1). Amphetamine is also believed to exert its effects by binding to the monoamine transporters (the dopamine transporter or DAT) and increasing extracellular levels of the biogenic amines dopamine, norepinephrine (noradrenaline) and serotonin.  The plasma elimination half-life of lisdexamfetamine typically averaged less than one hour.

A Patient has informs you that she has trouble swallowing pills and wants to know if it would be ok to dissolve the drug into water.

Will Hydrolysis interfere with the amide bond connecting lysine to d-amphetamine when stored at a temperature of 30C?



*I have the picture with the reference table as well as the chemical structure, but can't seem figure out how to upload a picture

[Arkcon]

Curious problem, lots of extraneous information.  OK.  Use the + Additional Options... options to attach an image.  Consider the structure, and that it requires liver enzymes to cleave the lysine, and see what you think about plain water cleaving the molecule.

[saved316]

Well I know that  the liver uses Adolase enzymes cleave off the lysine molecule, along with Tyrosine that acts as a hydrogen acceptor while the lysine covalently binds and stabilizes the intermediates and eventually results with dextroamphetamine being absorbed through the intestine. So H2O should have a negligible effect on the compound anywhere close to that temperature  correct?

[saved316]

Here we go

[Babcock_Hall]

Well I know that  the liver uses Adolase enzymes cleave off the lysine molecule, along with Tyrosine that acts as a hydrogen acceptor while the lysine covalently binds and stabilizes the intermediates and eventually results with dextroamphetamine being absorbed through the intestine. So H2O should have a negligible effect on the compound anywhere close to that temperature  correct?

Do you mean aldolase-type enzymes?  If the lysine is simply being cleaved, it looks more like an amidase reaction.