DRUG RECEPTORS

AND
DETERMINANTS OF
BIOLOGICAL
RESPONSES
 Agonist Drugs
• drugs that interact with and activate
receptors; they possess both affinity
and efficacy
• two types
–Full – an agonist with maximal
efficacy
–Partial – an agonist with less then
maximal efficacy
2004-2005
Agonist Dose
Response Curves

Full agonist
Partial agonist
Response

Dose
2004-2005
 Antagonist Drug

• Antagonists interact with the

receptor but do NOT change the
receptor
• they have affinity but NO efficacy
• two types
– Competitive
– Noncompetitive
2004-2005
Competitive antagonism

1. Competitive antagonist compete with the agonist in a

reversible fashion for the same receptor site
2. When the antagonist is present the log –dose response
curve is shifted to the right indicating that a higher
concentration of agonist is necessary to achieve the
same response as when the antagonist is absent
3. In the presence of the antagonist , if enough or a large
amount of agonist is given , the ( Emax) can be achieved ,
indicating that the action of the antagonist has been
overcome .
 Drug Receptor Interactions

Competitive
Inhibition

Antagonist Receptor

Antagonist-Receptor
DENIED!
Complex
Noncompetitive antagonism
1. The non competitive antagonist bind irreversibly
to the receptor site or to another site that inhibits
the response to the agonist
2. No matter how much agonist is given , the action
of the antagonist cannot be over come
3. This results in a nonparallel shift of the log dose
response curve with a lower Emax .
 Drug Receptor Interactions

Non-competitive
Antagonist
Inhibition

Agonist Receptor

DENIED!
‘Inhibited’-Receptor
 Drug-Receptor Interactions

• Traditional model was a rigid “Lock and Key”

– Lock  Receptor surface
– Key  Drug or Ligand

Drug

Receptor
Ion channel
receptors
Structure:
•Protein pores
in the plasma
membrane

2004-2005
 Structure:
1. G protein-linked receptors
•Single
polypeptide
chain threaded
back and forth
resulting in 7
transmembrane
å helices
•There’s a G
protein
attached to the
cytoplasmic
side of the
membrane
(functions as a
2004-2005 switch).
2004-2005
THIS GROUP INCLUDES RECEPTORS FOR
1. SEX HORMONES – ESTROGENS , ANDROGENS , PROGESTERONE
2. GLUCOCORTICOID
3. MINERALOCORTICOID
4. VITAMIN D
OTHER INTRACELLULAR RECEPTORS :
1. Thyroid hormone
2. Vitamin A
3. the Peroxisome Proliferator-Activated Receptors (PPARs) are a group
of nuclear receptor proteins that function as transcription factors
regulating the expression of genes. PPARs play essential roles in the
regulation of cellular differentiation, development, and metabolism
(carbohydrate, lipid, protein), and tumorigenesis of higher organisms.
.
Three types of PPARs have been identified: alpha, gamma,
and delta (beta):
1. alpha- expressed in liver, kidney, heart, muscle, adipose
tissue

2. β/δ (beta/delta) - expressed in many tissues but markedly

in brain, adipose tissue, and skin

3. γ (gamma)- this PPAR through alternative splicing is

expressed in three forms:

(a) γ1 - expressed in virtually all tissues, including

heart, muscle, colon, kidney,pancreas, and spleen
(b) γ2 - expressed mainly in adipose tissue
(c) γ3 - expressed in macrophages, large intestine,
white adipose tissue.
.
Endogenous ligands for the PPARs include free fatty
acids and eicosanoids.
• PPARγ is activated by PGJ2 (a prostaglandin).
• In contrast, PPARα is activated by leukotriene B4
PPARα and PPARγ are the molecular targets of a number of
marketed drugs.
1.the hypolipidemic fibrates activate PPARα,
2.the anti diabetic thiazolidinediones activate PPARγ