Page 121 - Medicinal Chemistry Self Assessment

110 Medicinal Chemistry Self Assessment

Biological Targets and Routes of Administration
Loperamide: µ opioid receptors located in the large intestine; oral administration
Scopolamine: muscarinic acetylcholine receptors (M1) located in the peripheral nervous system;
transdermal administration

Answer
Loperamide:
• Oral tablet is swallowed.

• Tablet dissolves in aqueous contents of the stomach (requires drug to be water soluble).
The amide, piperidine (tertiary amine), and tertiary alcohol have hydrophilic character and
contribute to the water solubility of the drug.
• Do not want absorption into systemic circulation via stomach lining.

The piperidine (tertiary amine pK =9–11) will be predominantly ionized in the stomach
a
pH=1 (pH < pK ).
a
• Distribution into intestine—smaller fraction in ionized form; retain water solubility.
The piperidine (tertiary amine pK =9–11) will be somewhat less (but still predominantly) ionized
a
in the intestine pH=8 (pH < pK ).
a
• Interaction with receptor located in intestine—there is no need for absorption out of the gastro-
intestinal (GI) system and into systemic distribution.

Scopolamine:
• Patch is placed on skin.
• Absorption of drug occurs from patch into skin lipophilic bilayer (requires hydrophobic
character).
The aromatic ring and bicyclic heterocycle contribute to hydrophobic character of the drug and
allow for absorption and transport through skin.

• Drug transports through skin and dissolves into circulation (requires drug to be water soluble).
The bicyclic heterocycle (tertiary amine pK =9–11) will be primarily ionized in the plasma pH=7.4
a
(pH < pK ). The ester, ether, and primary alcohol are hydrophilic in character and contribute to
a
the water solubility of the drug.
• Distribution to peripheral receptors (requires drug to be water soluble).
The bicyclic heterocycle (tertiary amine pK =9–11) will be primarily ionized in the plasma pH=7.4
a
(pH < pK ). The ester, ether, and primary alcohol are hydrophilic in character and contribute to
a
the water solubility of the drug.
• Interaction occurs with receptors located in periphery.