MDG5204 Chap.6 Drug Targets, Receptors and Selectivity
Drug Targets, Receptors and Selectivity
From kinetics to dynamics
Pharmacodynamics is the study of what a drug does to the body: its biochemical, cellular and physiological actions and the molecular mechanisms behind them. The lecture opens with a principle worth keeping in view throughout: drugs do not create new biological processes; they amplify, fine-tune or block existing ones.
A drug is a substance that elicits a biological effect, and a target is the site it binds to produce it.
What drugs bind to
Most targets are proteins, including cell-surface and intracellular receptors, enzymes, ion channels, transporters, pumps and structural proteins, and fewer are nucleic acids.
The course pairs each class with an example, from propranolol at the beta-adrenoceptor to lovastatin at HMG-CoA reductase and cisplatin at DNA.
It also shows pharmacology merging with immunology and genetics, through monoclonal antibodies, gene therapy, CAR T cells, small interfering RNA, antisense oligonucleotides and epigenetic drugs.
Receptors and binding
A receptor is a protein that recognises a signalling molecule native to the organism and turns that recognition into a cellular event.
The course names four receptor-effector families: ligand-gated ion channels, G protein-coupled receptors, kinase-linked receptors and nuclear receptors. Most drugs bind through weak, reversible forces, ionic, dipole, hydrogen-bond, van der Waals and hydrophobic interactions, which work only at very short range and impose strict structural requirements.
Covalent binding, as with afatinib at the EGFR, is strong and often irreversible. The chemical features essential for binding make up the pharmacophore, found by comparing analogues in structure-activity studies.
Selectivity and its consequences
Specificity means a ligand binds only one receptor type; selectivity means a preference for one target over the rest that depends on concentration.
Most drugs are selective rather than specific, and selectivity falls as concentration rises. The course's examples show why this matters: a beta-1 selective blocker spares the airway receptor a non-selective blocker hits, a first-generation antihistamine causes dry mouth through cholinergic block, and terfenadine's affinity for the hERG channel caused fatal arrhythmia that its more selective metabolite does not.
What this chapter covers
- 01
Drugs modulate existing biology rather than creating new processes
- 02
Protein and nucleic acid targets with one drug example for each
- 03
New modalities from monoclonal antibodies to gene silencing
- 04
Four receptor-effector families and the forces of drug binding
- 05
Structure-activity relationships and the pharmacophore
- 06
Selectivity against specificity, beta-blockers, antihistamines and hERG
Worked example · free
Choosing a beta-blocker for a patient with asthma
- 2Identify the receptor responsible for the wanted effect.
- 2Identify the receptor responsible for the risk.
- 2Choose the drug and state the limit on the choice.
Key terms
- Drug Target
- The molecule, usually a protein, to which a drug binds to produce its effect.
- Receptor
- A protein that recognises an endogenous signalling molecule and converts binding into a cellular event.
- Pharmacophore
- The arrangement of chemical features in a drug that is essential for binding to its receptor.
- Selectivity
- A drug’s preference for one target over the rest, based on relative affinity and weakening as concentration rises.
- Specificity
- Binding of a ligand to only one type of receptor, a chemical rather than a pharmacological idea.
- Ligand
- A molecule of the body’s own or from outside that attaches to a receptor.
Drug Targets, Receptors and Selectivity FAQ
Why do most drugs have side effects even when they are well designed?
Most drugs are selective rather than specific: they prefer one target but bind others at higher concentrations. As concentration rises that preference weakens, so off-target binding produces effects unrelated to the intended one, as with dry mouth from older antihistamines.
What is the difference between reversible and irreversible drug binding?
Reversible binding uses weak forces such as ionic, hydrogen-bond and hydrophobic interactions, so the drug leaves the target as its concentration falls. Irreversible binding forms a covalent bond, as with afatinib, so the effect persists until the cell makes new target protein.
Why was terfenadine replaced by fexofenadine?
Both block the H1 receptor equally well, but terfenadine also binds the hERG potassium channel strongly, which can prolong the QT interval and cause torsades de pointes. Fexofenadine binds hERG weakly, so it keeps the antihistamine effect with far less cardiac risk.
Exam move
Build a one-page table of target class, drug, action and use from memory, then add one sentence per row on what an off-target effect of that drug would look like. The second column is what turns recall into the reasoning the examination asks for.
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