Agonist-antagonist

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

Types of mixed agonist/antagonist include receptor 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 as selective receptor modulators).

Synaptic receptors

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 time neurotransmitters 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 is reuptake 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 the

• mu opioid receptor (μ)^[4]
• delta opioid receptor (δ)^[5]
• nalbuphine, κ-agonist/μ-antagonist analgesic^[6]

Agonist–antagonist opioids usually have a

• Competitive antagonist
• Inverse agonist
• Partial agonist

References