DRUG RECEPTOR INTERACTIONS:

DRUG:

According to WHO definition:

“Drug is any substance or product that is used or is intended to be used to modify or explore

physiological systems or pathological states for the benefit of the recipient.”

All chemicals are not drugs but all drugs are chemicals.

The ability of a drug to attach to a receptor is mediated by its chemical structure, which allows it to
interact with complementary receptor surfaces.

The agonist activates or boosts cellular activity after it binds to the receptor. Medications that bind to
beta receptors in the heart and enhance the force of myocardial contraction, or drugs that bind to alpha
receptors on blood arteries and raise blood pressure, are examples of agonist activity.

RECEPTOR:

A receptor is a chemical component of a cell that interacts with a drug to create its pharmacological
effects.

Specific regions of proteins and nucleic acids have been identified as receptor sites.

The cellular macromolecule macromolecular complex with which the drug interacts to elicit a cellular
response, i.e. a change in cell function, is referred to as the drug receptor or drug target.

D+R DR=RESPONSE

A receptor has two configurations as of a switch: “ON” and “OFF”

There are four primary receptor families which are listed below:

Ligand gated Ion Channel

G-protein coupled Receptor Systems

Enzyme-linked receptors

Intracellular receptors

DRUG-RECEPTOR INTERACTIONS:
Some of the important interactions which are involved in the drug-receptor complex are:

Covalent bonding

Ionic interactions

Hydrogen bonding

Hydrophobic interactions

Vander Waals interactions

Dipole-dipole interactions

Covalent Bonds

 The covalent bond is the strongest type of bond, and it is produced when two atoms share
electrons.
 Except for enzymes and DNA, it is produced via a drug–receptor interaction.
 The majority of drugs bind to their receptors through weak molecular interactions, which
create a strong bond between the drug and its receptor but are reversible on their own.
 In comparison to other bonds, covalent bonds are crucial.

Ionic (or Electrostatic) Interactions

At physiological pH (pH 7.4), basic groups like the amino side chains of arginine and lysine are
protonated and provide a cationic environment for protein receptors.

Acidic groups, such as the carboxylic acid side chains of aspartic acid and glutamic acid, are
deprotonated to give anionic groups.

Drug and receptor groups will be mutually attracted provided they have opposite charges. This ionic
interaction can be effective at distances farther than those required for other types of interactions, and
they can persist longer.

Ion–Dipole and Dipole–Dipole Interactions

 As a result of the greater electronegativity of atoms such as oxygen, nitrogen, sulfur, and halogens
relative to that of carbon, C–X bonds in drugs and receptors, where X is an electronegative atom, will
have an asymmetric distribution of electrons; this produces electronic dipoles.

 These dipoles in a drug molecule can be attracted by ions (ion–dipole interaction) or by other
dipoles (dipole–dipole interaction) in the receptor, provided charges of opposite sign are properly
aligned.
Because the charge of a dipole is less than that of an ion, a dipole–dipole interaction is weaker than an
ion– dipole interaction.

Hydrogen Bonds

 Hydrogen bonds are a type of dipole–dipole interaction formed between the proton of a group X–H,
where X is an electronegative atom, and one or more other electronegative atoms (Y) containing a
pair of non-bonded electrons.

 The most significant hydrogen bonds occur in molecules where X and Y are N and O .

 X removes electron density from the hydrogen so it has a partial positive charge, which is strongly
attracted to the non-bonded electrons of Y. The interaction is denoted as a dotted line, –X–H----Y–

 X is referred to as the hydrogen bond donor and Y is the hydrogen bond acceptor. When X and Y
are equivalent in electronegativity and degree of ionization, the proton can be shared equally between
the two groups, i.e. –X---H---Y–.

CHARGE-TRANSFER COMPLEXES:

When an electron donor molecule (or group) comes into touch with an electron acceptor molecule (or
group), the donor may transfer some of its charge to the acceptor. This results in the formation of a
charge-transfer complex.

Alkenes, alkynes, and aromatic moieties with electron-donating substituents are examples of donor
groups, as are groups containing a pair of non-bonded electrons, such as oxygen, nitrogen, and
sulphur moieties.

Electron-deficient -orbitals, such as alkenes, alkynes, and aromatic moieties with electron-
withdrawing substituents, are found in acceptor groups, as are weakly acidic protons.

The aromatic ring of tyrosine and the carboxylate group of aspartate are examples of groups on
receptors that can act as electron donors.

HALOGEN BONDING:

The ability of a covalently linked halogen atom to operate as an electron acceptor (Lewis acid) for
halogen bonding with an electron-rich donor atom, such as O, N, or S, has long been known.

These interactions can influence the conformation of molecules in a protein's binding site.

VANDER WAALS FORCES:

In nonpolar molecules, atoms may have a brief non-symmetrical electron density distribution,
resulting in the production of a temporary dipole.
The temporary dipoles of one molecule produce opposite dipoles in the approaching molecule as
atoms from different molecules (such as a drug and a receptor) approach one other. Intermolecular
attractions, also known as van der Waals forces, result as a result.

Only when the atoms are in close surface contact do these weak universal forces become relevant.

AGONIST:

Agonists are substances that activate receptors and are drugs with high intrinsic activity and affinity.

Many medications work as agonists to achieve their effects.

Dobutamine, for example, replicates the action of nor-ephenephrine at the heart's receptors. As a
result, the heart contracts and the heart rate rises.

An agonist binds to a receptor and causes it to respond biologically.

Full agonists,

partial agonists, and

reverse agonists are all types of agonists.

Full agonist: A full agonist is a substance that binds to a receptor and provides a maximal biological
response that mirrors the response to the endogenous ligand.

The receptor is stabilized in its active state when a full agonist is used.

Partial agonist: Efficacies that are greater than zero but not as high as a full agonist.

A partial agonist might have an affinity that is higher, lower, or equal to that of a full agonist.

Inverse agonists produce responses that are lower than those assessed in the absence of the
medication.

This reduces the number of active receptors to levels lower than those seen when the medication is not
present.

They have the pharmacological effect of antagonists to receptor agonists.

Antagonists are medications that block the effects of another drug or a naturally occurring ligand. If
an agonist isn't present, an antagonist has no impact.
Antagonists have no effect on their own.
Competitive antagonists are adversaries who are able to outperform one other.
antagonists that are non-competetive (irreversible)
Competitive antagonists are antagonists and agonists that bind to the same receptor.
the receptor's location
Non-competitive antagonists: An irreversible antagonist produces a reversal of the situation.
The maximum has shifted downward. And it's not something that can be fixed by adding more.
more of an agonist
Covalent binding to the receptor's active site
Allosteric binding is the second type of binding.

Sl.N Competitive antagonist Non-competitive antagonists

o
1. Antagonist binds with the same Binds to another site of
receptor as the agonist receptor
2. Antagonist resembles chemically Does not resemble
with the agonist
3. The same maximal response can be attained by Maximal response is
increasing dose of supported
agonist.

4. Right shift of agonist DRC Flattening of agonist DRC

5. Intensity of response depends on Depends only on conc. of
conc. of both agonist and antagonist
antagonist
6. Examples: ACh- Atropine Diazepam-Bicuculline
Morphine- Naloxone
 CHARACTERISTICS OF DRUG-RECEPTOR INTERACTIONS:

1. Follow Mass-Action Law: rate of reaction is DIRECTLY proportional to the concentration

of the reactants, however, there is a limit. This limit is called the point of saturation
o There are only so many receptors on each cell to which a drug can bind. Point of
saturation refers to the point at which every receptor is bound.
2. Selectivity: every drug has a preferred receptor; however, it may bind to others with the
same or lesser affinity than its preferred receptor. Side effects of drugs are a direct result of
low selectivity because one drug can bind multiple receptors producing undesired biological
responses.
o Not to be confused with “specificity” meaning drug can only bind to one type of receptor,
regardless of the drug dose: drugs that are “specific” are unheard of at this point
3. Response is Proportional to Drug Dose [Concentration] up to the point of saturation

4. Binding Changes the Receptor: when a drug binds a receptor it results in one of two
changes as outlined below:
o AGONIST: results in an active receptor conformation to produce desired biological effect,
i.e. intracellular signaling or changes in organ function
5. ANTAGONIST: a simple occupancy by the antagonist of the receptor to hinder access of
an agonist to its binding site on the receptor, therefore, obliterating the response to the
agonist.