Organic Chemistry

1214 CHAPTER 30 The Organic Chemistry of Drugs

30.6 Receptors

Many drugs exert their physiological effects by binding to a specific cellular

binding site called a receptor. That is why a small amount of a drug can bring about

a measurable effect. Drug receptors are often glycoproteins or lipoproteins, which

explains why different enantiomers of a drug have different effects (Section 5.15).

Some receptors are part of cell membranes, while others are found in the

cytoplasm—the material outside the nucleus. Because not all cells have the same re-

ceptors, drugs have considerable specificity. For example, epinephrine has intense

effects on cardiac muscle, but almost no effect on muscle in other parts of the body.

Nucleic acids—particularly DNA—also act as receptors for certain kinds of drugs.

A drug interacts with its receptor by means of the same kinds of bonding

interactions—hydrogen bonding, electrostatic attractions, and van der Waals inter-

actions—that we encountered in other examples of molecular recognition

(Section 24.8). The most important factor in bringing together a drug and a recep-

tor is a snug fit: The greater the affinity of a drug for its binding site, the higher is

the drug’s potential biological activity. Two drugs for which DNA is a receptor are

chloroquine (an antimalarial) and 3,6-diaminoacridine (an antibacterial). These flat

cyclic compounds can slide into the DNA double helix between base pairs—like a

card being inserted into a deck of playing cards—and interfere with the normal

replication of DNA.

Knowing something about the molecular basis of drug action—such as how a drug

interacts with a receptor—allows scientists to design and synthesize compounds that

might have a desired biological activity. For example, when excess histamine is pro-

duced by the body, it causes the symptoms associated with the common cold and

allergic responses. This is thought to be the result of the protonated ethylamino group

anchoring the histamine molecule to a negatively charged portion of the histamine

receptor.

−

histamine

N

N

H

CH 2 CH 2 NH 3

+

histamine

receptor

HNCHCH 2 CH 2 CH 2 N

CH 2 CH 3

CH 2 CH 3

Cl N

chloroquine

H 2 NNHN 2

3,6-diaminoacridine

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