What is a partial agonist receptor?

From the Guidelines

A partial agonist receptor is a drug or compound that binds to a receptor and activates it, but produces only a partial response compared to a full agonist, even at maximum concentration. This is evident in the case of buprenorphine, a partial mu opioid receptor agonist, which has a high binding affinity and mimics antagonist properties at higher doses 1. When a partial agonist binds to a receptor, it stimulates the receptor to a lesser degree than a full agonist would, typically achieving between 20-80% of the maximum possible effect.

Some key characteristics of partial agonist receptors include:

• Binding to a receptor and activating it, but producing only a partial response
• Stimulating the receptor to a lesser degree than a full agonist would
• Achieving between 20-80% of the maximum possible effect
• Having a ceiling effect for both therapeutic and adverse outcomes, potentially creating a wider therapeutic window and improved safety profile compared to full agonists

Examples of partial agonists include:

• Buprenorphine, a partial opioid agonist used for pain and addiction treatment 1
• Aripiprazole, a partial dopamine agonist used as an antipsychotic
• Varenicline, a partial nicotinic receptor agonist used for smoking cessation

The unique property of partial agonists makes them valuable in medicine because they can act as either an activator or blocker depending on the surrounding conditions, as seen in the case of buprenorphine, which has been used for opioid detoxification, addiction therapy, acute pain, and chronic pain management in the USA since 2002 1.

From the Research

Definition of Partial Agonist Receptor

• A partial agonist is a substance that elicits a lower maximal response of a particular biological system than a defined standard, typically a full agonist 2.
• Partial agonists cannot induce full responses, unlike full agonists, and their effect is relative to the standard substance 3.
• The definition of a partial agonist rests on the definition of a standard substance that achieves a 'full' maximal response, with partial agonism being relative 2.

Mechanisms of Partial Agonism

• Various mechanisms lie behind partial agonism, including receptor-related mechanisms and mechanisms based on the efficacy of the stimulus-response coupling 2.
• Receptor-related mechanisms involve the agonist-receptor complex existing in several conformational states, with only one or a few activating the cell signaling pathway 2.
• The efficacy of the stimulus-response coupling is proportional to the sum of probabilities that receptors in individual states activate the cell-signaling pathway 2.

Examples of Partial Agonists

• Buprenorphine is a partial agonist at the μ-opioid receptor, with high binding affinity and unique pharmacodynamic and pharmacokinetic properties 4.
• Buprenorphine's partial agonism does not provide partial analgesia, but rather analgesia equivalent to that of full μ-opioid receptor agonists 4.
• Other partial agonists, such as butorphanol and nalbuphine, have been studied in the context of opioid addiction and analgesia 5.

Characteristics of Partial Agonists

• Partial agonists produce bell-shaped concentration-response curves or concentration-response curves with reduced but plateaued maximum responses 6.
• The potency and maximum activity of partial agonists are predictable based on the receptor binding affinities of the incorporated agonist and antagonist 6.
• Partial agonists can be useful for therapeutic purposes, enabling stable activation of a specific type of receptor at desired submaximal set-points 6.