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.
Agonist–antagonist opioids usually have a
ceiling 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 produce
psychotomimetic effects.[8]
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^Del Bello F, Mattioli L, Ghelfi F, Giannella M, Piergentili A, Quaglia W, et al. (November 2010). "Fruitful adrenergic α(2C)-agonism/α(2A)-antagonism combination to prevent and contrast morphine tolerance and dependence". Journal of Medicinal Chemistry. 53 (21): 7825–35.
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^Hollister LE (17 July 1991). "AMA Drug Evaluations Annual 1991". JAMA: The Journal of the American Medical Association. 266 (3): 97.
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^Schmidt WK, Tam SW, Shotzberger GS, Smith DH, Clark R, Vernier VG (February 1985). "Nalbuphine". Drug and Alcohol Dependence. 14 (3–4): 339–62.
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^Benson GJ, Tranquilli WJ (March 1992). "Advantages and guidelines for using opioid agonist-antagonist analgesics". The Veterinary Clinics of North America. Small Animal Practice. 22 (2): 363–5.
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