Page 202 - Medicinal Chemistry Self Assessment

2.19 Lidocaine 191

4. Unless excreted unchanged, drug molecules undergo one or more metabolic transformations to
deactivate the drug and/or make the drug sufficiently water soluble to permit elimination. There are
a variety of transformations that are possible for most drugs, but only the minimum number of trans-
1.19 and 2.19 – remove bold from labels and remove answers from over the arrows (pay no attention to
formations actually occurs. The following diagram captures the metabolic pathways for lidocaine
the colors)
that are observed clinically. For each transformation, identify which phase I metabolic transformation
has taken place next to the relevant arrow.

Answer
CH CH 3
3
O
N CH 3
N
CH 3 H

Lidocaine

H O CH CH 3 CH 3 O H
3
O N CH
N CH 3 N 3
N
CH H
CH 3 H 3

Monoethylglycinexylidide

H O CH 3
O H
N CH 3
N

CH 3 H CH CH
3
3
O
NH 2
3-Hydroxy-monoethylglycineexylidide NH 2 N
CH 3 CH 3 H

+ Glycinexylidide
O H
N CH 3
H O

5. Now that you have identified the metabolic transformations that generate products that have been
identified, put your detective hat on and list any additional phase I transformations that could have
occurred.

Answer
Benzylic oxidation (on either or both of the aromatic ring methyl substituents). The resulting primary
alcohol can subsequently undergo alcohol oxidation to the corresponding aldehyde. The aldehyde
then undergoes aldehyde oxidation to the corresponding carboxylic acid.