Chapter 2: Drug Receptors & proteins are also important drug targets, such as tubulin,

the receptor for the anti-inflammatory agent colchicine.

Pharmacodynamics

receptor: the component of a cell or organism that

interacts with a drug and initiates the chain of events
leading to the drug’s observed effects

1. Receptors largely determine the quantitative relations

between dose or concentration of drug and
pharmacologic effects. The
receptor’s affinity for binding a drug determines the
concentration of drug required to form a significant
number of drug-receptor complexes, and
the total number of receptors may limit the maximal
effect a drug may produce.
2. Receptors are responsible for selectivity of drug
action. The molecular size, shape, and electrical charge
of a drug determine whether—and
with what affinity—it will bind to a particular receptor
among the vast array of chemically different binding
sites available in a cell, tissue, or patient.
Accordingly, changes in the chemical structure of a drug
can dramatically increase or decrease a new drug’s
affinities for different classes of
receptors, with resulting alterations in therapeutic and
toxic effects.
3. Receptors mediate the actions of pharmacologic
agonists and antagonists. Some drugs and many natural
ligands, such as hormones
and neurotransmitters, regulate the function of receptor
macromolecules as agonists; this means that they
activate the receptor to signal as a
direct result of binding to it

antagonists; that is, they bind to receptors but do not

activate generation of a signal; consequently, they
interfere
with the ability of an agonist to activate the receptor

MACROMOLECULAR NATURE OF DRUG

RECEPTORS

almost all of the receptors that we discuss in this

chapter, are proteins.

regulatory proteins, which mediate the actions of

endogenous chemical signals such as
neurotransmitters, autacoids, and hormones

Enzymes may be inhibited (or, less commonly,

activated) by binding a drug.
Examples include dihydrofolate reductase, the receptor
for the antineoplastic drug methotrexate; 3-hydroxy-3-
methylglutaryl–coenzyme A (HMG-CoA)
reductase, the receptor for statins; and various protein
and lipid kinases. Transport proteins can be useful drug
targets. Examples include Na+
/K+-
ATPase, the membrane receptor for cardioactive
digitalis glycosides; norepinephrine and serotonin
transporter proteins that are membrane receptors
for antidepressant drugs; and dopamine transporters
that are membrane receptors for cocaine and a number
of other psychostimulants. Structural