Drug Receptors

How drugs work

1. bind to target molecule/receptor

2. causes chemical or metabolic change in property of cell

3. does not create new cell effects/actions!

Drug receptors

• proteins on/in a cell surface/cytoplasm

Ligand

• something that binds a receptor

Ionotropic vs metabotropic receptors

• forms ion channels to allow flow, fast-acting (milliseconds) (ex: GABA receptor)

vs

• linked to other enzymes/2nd messengers, slower onset of action (seconds), indirectly linked to ion channels (ex: GPCRs)

Signal transduction via receptors

• ion channel: open/close

• GCPRs: increase/decrease enzyme action

• enzyme-linked

• intracellular/nuclear

Ion channels

• pores formed in cell membrane

• may be voltage- or ligand-gated

• ionotropic

GPCRs

• 3 subunits (alpha, beta, gamma)

• targets for majority of veterinary drugs

• binding of receptor to ligand activates protein, which then activates or inhibits an enzyme, ion channel, or other target

• different effect by subtype (s, i, & q subtypes)

• metabotropic

Enzyme-lined receptors

• transmembrane receptors with extracellular binding sites

• receptors form heterodimers

• activated receptor autophosphorylates, generating cell signaling

• metabotropic

Intracellular receptors

• drug enters cytoplasm & alters DNA, changing action of cell

• metabotropic

Activity

• intrinsic ability of drug to create response

Affinity

• force of attraction between drug & receptor

• tendency to bind to a receptor

Selectivity

• a drug’s ability to affect a particular receptor population in preference to others

Agonists

• bind receptors & cause response

• mimic activity of endogenous substances

Partial agonists

• bind & activate receptors

• only results in partial response (maximal not observed)

  • drug has slightly different shape to regular ligand

Antagonists

• bind receptors & do NOT cause a response

• block a receptor, usually via competition

• can still have affinity of receptor

• usually reversible (unless covalently bonded)

Inverse agonist

• binds to receptor and has opposite effect of normal

• ex: antihistamines

Competitive vs non-competitive antagonists

• looks like the ligand & binds at same site

vs

• binds elsewhere & changes conformation so agonist can’t bind

Efficacy

• maximum response level due to intrinsic activity

Potency

• amount of drug needed to produce effect

Therapeutic effect

• between minimal effective level & toxic level