Antagonists are drugs that interact selectively with receptors but
do not lead to an observed effect. Instead they reduce the action
of an agonist at the receptor site involved.
DRUG: A chemical agent that selectively interacts with specific target
molecules (i.e. receptors) to alter their specific physiological
functions.
Agonist: drug that activates receptors to result in either stimulation
or inhibition of the function of various types of cells and organs.
Antagonist: A chemical substance that binds to and blocks the
activation of receptors on cells, preventing a biological response.
cimetidine is an antagonist drug because it binds to the receptor site
in the stomach otherwise histamine will bind to the receptor site and
induce the secretion of HCl in the stomach. Thus, this antacid blocks
the receptor site and hence, the secretion of HCI is reduced thereby
reducing/removing hyperacidity.
Drug action-receptor theory
Medicinal chemists use the techniques of chemical synthesis &
computational drug design to insert new chemical groups into the
biomedical compound and test the modifications for their biological
effects. This method was refined to build mathematical relationships
between the chemical structure and the biological activity, known as
quantitative structureactivity relationships (QSAR).
There are several ways to explain SAR in drug receptor interaction:
1. Molecular Docking: This computational method involves studying
how the three-dimensional structure of a drug molecule fits into
the binding site of a receptor. It helps in understanding how
specific structural features of the drug interact with the receptor
to produce a biological effect.
2. Quantitative Structure-Activity Relationship (QSAR): QSAR is a
modeling technique that correlates the chemical structure of a
drug with its biological activity. By analyzing a series of structurally
related compounds and their corresponding activities, QSAR can
help identify the essential structural elements responsible for the
activity.
3. Drug Design: Understanding SAR is crucial in rational drug design,
where scientists modify the chemical structure of a drug to
optimize its interaction with the receptor, resulting in improved
efficacy and reduced side effects.
binding role of –OH group
OH group are common in drugs and are often involved in hydrogen
bonding, the oxygen as a H-bond acceptor (HBA) and the hydrogen as
hydrogen-bond donor (HBD). Converting the hydroxyl into
an ether or ester, as H-bonding would be disrupted in either of these
derivatives.
binding role of aromatic rings
Aromatic rings are planar, hydrophobic structures, commonly involved
in van der Waals and hydrophobic interactions with flat hydrophobic
regions of the binding site. The saturated analogue (e.g. cyclohexane
instead of benzene) may not bind so well as the ring is no longer flat —
the axial protons can interact weakly, but will act as buffers, keeping
the rest of the cyclohexane ring at a distance. The binding region for
the aromatic ring may also be a narrow slot rather than a planar
surface, in which case the cyclohexane ring would be unlikely to bind
as it is too bulky.
binding role of NH2 group
Amines are very important functional groups in medicinal chemistry
and are present in many drugs. They may be involved in H-bonding
either as an HBA or an HBD.