Agonists

• A partial agonist can never produce a maximal response at a receptor, otherwise it would be a full agonist
• Partial agonists can have the same affinity for a receptor as a full agonist (although generally they have lower affinity for the receptor)
• If a partial agonist does have the same affinity for a receptor as a full agonist, it will have the same equilibrium constant (K_A or K_D)

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

• This dose-response curve demonstrates the difference between a full and a partial agonist with similar potency
• The partial agonist demonstrates submaximal efficacy (i.e. unable to cause 100% population response)
• There is also a reduced gradient of the curve
• However, the potency (ED₅₀) is similar; the best response the partial agonist can exert is 50% of the population, therefore its ED₅₀ is at 25% response

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

• This dose-response curve shows partial agonists with different potencies
• Partial agonist B has higher potency i.e. lower ED₅₀, although its efficacy is still less
• Conversely, partial agonist C has a lower potency i.e. higher ED₅₀, and also has lower efficacy

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

• This curve demonstrates that partial agonists can act as antagonists


• Line A
• There is no full agonist present at baseline
• Increasing doses of partial agonist cause an increasing response up to the partial agonist's maximum efficacy
• I.e. the partial agonist is acting as an agonist


• Lines B-D
• An increasing amount of full agonist is present
• The partial agonist can still act as an agonist in the presence of some full agonist


• Line H
• There is a high full agonist concentration at baseline, causing 100% response
• Increasing the dose of partial agonist causes a decreasing response because it displaces the full agonist from receptors
• This therefore prevents the maximum response as would have been seen with the full agonist alone
• I.e. the partial agonist is acting as a competitive antagonist

Adapted from Physics, Pharmacology and Physiology for Anaesthetists

• An inverse agonist is a drug which, when bound to a specific receptor, produces the opposite effect to the endogenous agonist
• E.g. atropine at the muscarinic acetylcholine receptor vs. Ach
• E.g. naloxone