3.1 Drug-Receptor Interactions

Drug-receptor interactions are the molecular basis of drug action. Understanding binding kinetics and receptor properties is essential for rational drug design.

Receptor Types

G-Protein Coupled (GPCRs)

7-transmembrane domain. Signal via G-proteins. ~30% of drug targets. Seconds to minutes response.

Ion Channels

Ligand-gated or voltage-gated. Millisecond response. Nicotinic ACh, GABA-A, glutamate receptors.

Enzyme-Linked

Receptor tyrosine kinases. Insulin, growth factors. Minutes to hours response.

Nuclear Receptors

Transcription factors. Steroids, thyroid hormone. Hours to days response.

Binding Equilibrium

\( [D] + [R] \rightleftharpoons [DR] \)

\( K_d = \frac{[D][R]}{[DR]} = \frac{k_{off}}{k_{on}} \)

Kd = dissociation constant. Lower Kd = higher affinity. Concentration at 50% receptor occupancy.

Key Concepts

Affinity

Strength of drug-receptor binding. Measured by Kd.

Efficacy

Ability to activate receptor. Intrinsic activity (0-1).

Potency

Drug concentration for given effect. EC50 or ED50.

Selectivity

Preference for one receptor over others.