In pharmacology the termagonist-antagonist ormixed agonist/antagonist is used to refer to a drug which under some conditions behaves as anagonist (a substance that fully activates the receptor that it binds to) while under other conditions, behaves as anantagonist (a substance that binds to a receptor but does not activate and can block the activity of other agonists).

Types of mixed agonist/antagonist includereceptor ligands that act as agonist for some receptor types and antagonist for others^[1] or agonist in some tissues while antagonist in others (also known asselective receptor modulators).

For synaptic receptors, an agonist is a compound that increases the activation of the receptor by binding directly to it or by increasing the amount of timeneurotransmitters are in the synaptic cleft. An antagonist is a compound that has the opposite effect of an agonist. It decreases the activation of a synaptic receptor by binding and blocking neurotransmitters from binding or by decreasing the amount of time neurotransmitters are in the synaptic cleft. These actions can be achieved via multiple mechanisms. A common mechanism for agonists isreuptake inhibition, where the agonist blocks neurotransmitters from reentering the pre-synaptic axon terminal. This gives the neurotransmitter more time in the synaptic cleft to act on the synaptic receptors. Conversely, antagonists often bind directly to receptors in the synaptic cleft, effectively blocking neurotransmitters from binding.

At thealpha adrenoceptors,(R)-3-nitrobiphenyline is an α_2C selective agonist as well as being a weakantagonist at the α_2A and α_2B subtypes.^[2][3]

The best known agonist-antagonists areopioids. Examples of such opioids are:

• pentazocine, agonist at thekappa (κ) andsigma (σ) with weak antagonist action at themu opioid receptor (μ)^[4]
• butorphanol, pure agonist at κ-opioid receptor, partial agonist at μ-opioid receptor, and antagonist activity at thedelta opioid receptor (δ)^[5]
• nalbuphine, κ-agonist/μ-antagonist analgesic^[6]

Agonist–antagonist opioids usually have aceiling effect – over particular dose they don't increase their potency.^[7] Hence agonist–antagonist opioids have a lower addiction potential but also lower analgesic efficacy and are more likely to producepsychotomimetic effects.^[8]

Agonist–antagonist opioids that activatemu opioid receptors while blockingdelta produce analgesia without the development oftolerance.^[9]

• Competitive antagonist
• Inverse agonist
• Partial agonist

• Pharmacodynamics

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