{{Short description|Type of drug}} alt=The figure shows the difference in action between an agonist and an antagonist, compared to native neurotransmitter function.|thumb|209x209px|Agonist vs. 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. Which is a substance that fully activates and causes resultant cellular changes in the receptor that it binds to while producing an effect within the cell. While under other conditions, behaves as an antagonist where instead of activating the receptor that it binds to, it blocks the receptor to a natural agonist.<ref name=bp>{{cite journal |last1=Pleuvry |first1=Barbara |title=Receptors, agonists and antagonists. |journal=Anesthesia and Intensive Care Medicine |volume=5 |issue=10 |date=October 1, 2004 |pages=350-352 |url=https://doi.org/10.1383/anes.5.10.350.52312 |doi=10.1383/anes.5.10.350.52312 |access-date=April 18, 2026|url-access=subscription }}</ref>
Types of mixed agonist/antagonist include receptor ligands that act as agonist for some receptor types and antagonist for others<ref name="pmid1711441">{{cite journal |vauthors=Hoskin PJ, Hanks GW |title=Opioid agonist-antagonist drugs in acute and chronic pain states |journal=Drugs |volume=41 |issue=3 |pages=326–44 |date=March 1991 |pmid=1711441 |doi=10.2165/00003495-199141030-00002 |s2cid=27694903}}</ref> or agonist in some tissues while antagonist in others (also known as selective receptor modulators).
A '''Full agonist''' can produce the largest response that the tissue is capable of giving. When an agonist is a high-efficacy agonist it produces a maximum response even when it occupies a small proportion of receptors. On the other hand, a '''partial agonist''' does not have the ability to fully activate the receptors to where it is unable to provide a maximum response.<ref name=bp/>
==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 alpha adrenoceptors, (''R'')-3-nitrobiphenyline is an α<sub>2C</sub> selective agonist as well as being a weak antagonist at the α{{sub|2A}} and α{{sub|2B}} subtypes.<ref name="pmid17630725">{{cite journal |vauthors=Crassous PA, Cardinaletti C, Carrieri A, Bruni B, Di Vaira M, Gentili F, Ghelfi F, Giannella M, Paris H, Piergentili A, Quaglia W, Schaak S, Vesprini C, Pigini M |display-authors=6 |title=Alpha2-adrenoreceptors profile modulation. 3.1 (R)-(+)-m-nitrobiphenyline, a new efficient and alpha2C-subtype selective agonist |journal=Journal of Medicinal Chemistry |volume=50 |issue=16 |pages=3964–8 |date=August 2007 |pmid=17630725 |doi=10.1021/jm061487a}}</ref><ref>{{cite journal |vauthors=Del Bello F, Mattioli L, Ghelfi F, Giannella M, Piergentili A, Quaglia W, Cardinaletti C, Perfumi M, Thomas RJ, Zanelli U, Marchioro C, Dal Cin M, Pigini M |display-authors=6 |title=Fruitful adrenergic α(2C)-agonism/α(2A)-antagonism combination to prevent and contrast morphine tolerance and dependence |journal=Journal of Medicinal Chemistry |volume=53 |issue=21 |pages=7825–35 |date=November 2010 |pmid=20925410 |doi=10.1021/jm100977d}}</ref>
==Agonist-antagonist opioids==
The best known agonist-antagonists are opioids. Examples of such opioids are: * pentazocine, agonist at the kappa (κ) and sigma (σ) with weak antagonist action at the mu opioid receptor (μ)<ref>{{cite journal |last1=Hollister |first1=Leo E. |name-list-style=vanc |title=AMA Drug Evaluations Annual 1991 |journal=JAMA: The Journal of the American Medical Association |date=17 July 1991 |volume=266 |issue=3 |page=97 |doi=10.1001/jama.1991.03470030126039}}</ref> * butorphanol, pure agonist at κ-opioid receptor, partial agonist at μ-opioid receptor, and antagonist activity at the delta opioid receptor (δ)<ref name="pmid15942128">{{cite journal |vauthors=Commiskey S, Fan LW, Ho IK, Rockhold RW |title=Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors |journal=Journal of Pharmacological Sciences |volume=98 |issue=2 |pages=109–16 |date=June 2005 |pmid=15942128 |doi=10.1254/jphs.CRJ05001X |doi-access=free}}</ref> * nalbuphine, κ-agonist/μ-antagonist analgesic<ref name="pmid2986929">{{cite journal |vauthors=Schmidt WK, Tam SW, Shotzberger GS, Smith DH, Clark R, Vernier VG |title=Nalbuphine |journal=Drug and Alcohol Dependence |volume=14 |issue=3–4 |pages=339–62 |date=February 1985 |pmid=2986929 |doi=10.1016/0376-8716(85)90066-3}}</ref>
Agonist–antagonist opioids usually have a ceiling effect – over particular dose they don't increase their potency.<ref name="pmid1585578">{{cite journal |vauthors=Benson GJ, Tranquilli WJ |title=Advantages and guidelines for using opioid agonist-antagonist analgesics |journal=The Veterinary Clinics of North America. Small Animal Practice |volume=22 |issue=2 |pages=363–5 |date=March 1992 |pmid=1585578 |doi=10.1016/S0195-5616(92)50637-4}}</ref> Hence agonist–antagonist opioids have a lower addiction potential but also lower analgesic efficacy and are more likely to produce psychotomimetic effects.<ref name="pmid2894291">{{cite journal |vauthors=Lasagna L |title=Benefit-risk ratio of agonist-antagonist analgesics |journal=Drug and Alcohol Dependence |volume=20 |issue=4 |pages=385–93 |date=December 1987 |pmid=2894291 |doi=10.1111/j.1360-0443.1989.tb00595.x |doi-access=free}}</ref>
Agonist–antagonist opioids that activate mu opioid receptors while blocking delta produce analgesia without the development of tolerance.<ref name="pmid19474215">{{cite journal |vauthors=Dietis N, Guerrini R, Calo G, Salvadori S, Rowbotham DJ, Lambert DG |title=Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile |journal=British Journal of Anaesthesia |volume=103 |issue=1 |pages=38–49 |date=July 2009 |pmid=19474215 |doi=10.1093/bja/aep129 |doi-access=free}}</ref>
==See also== * Competitive antagonist * Inverse agonist * Partial agonist
==References== {{Reflist|33em}}
{{DEFAULTSORT:Agonist-antagonist}} Category:Pharmacodynamics