Cellular Drug Targets - In-depth Notes

Learning Objectives

  • Identify main types of target molecules for drug action.

  • Provide drug class examples and their mechanisms.

Historical Context

  • John Newport Langley and Paul Ehrlich pioneered the receptor concept, leading to an understanding of drugs' specificity.

  • Otto Loewi, Sir Henry Dale, and Humphrey Rang advanced receptor and neurotransmitter research, with Loewi identifying acetylcholine as a neurotransmitter.

Types of Drug Targets

  • Ion Channels: Gateways in membranes; drugs act as blockers/modulators.

    • Types: Ligand-gated and voltage-gated channels.

  • Enzymes: Targeted by drugs as competitive inhibitors or false substrates, influencing enzyme activity.

  • Transporters: Facilitate ion/molecule movement; drugs can inhibit transport, causing accumulation.

Types of Receptors

  1. Ligand-gated Ion Channels: Rapid synaptic events; examples include nicotinic acetylcholine and GABA receptors.

  2. G-Protein-Coupled Receptors (GPCRs): Largest family, involved in diverse processes; examples include muscarinic acetylcholine receptors.

  3. Kinase-Linked Receptors: Respond to proteins and regulate transcription, slower acting; includes insulin receptors.

  4. Nuclear Receptors: Intracellular, directly interacting with DNA; includes steroid receptors.

Summary of Receptors

Type

Location

Effector

Coupling

Examples

Structure

Ligand-gated Ion Channels

Membrane

Ion channel

Direct

Nicotinic acetylcholine, GABA

Oligomeric assembly with central pore

GPCRs

Membrane

Channel/enzyme

G protein

Muscarinic acetylcholine, Adrenoceptors

7 TM helices assembly

Kinase-Linked

Membrane

Protein kinases

Direct

Insulin, growth factors

Single transmembrane helix

Nuclear Receptors

Intracellular

Gene transcription

Via DNA

Steroid receptors

Monomeric with receptor- and DNA-binding regions

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References

  • Rang & Dale's Pharmacology.