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).
Agonist-antagonist opioids
The best known agonist-antagonists are opioids. Examples of such opioids are:
- pentazocine, agonist at the kappa (κ) and sigma (σ) and has a weak antagonist action at the mu opioid receptor (μ).[2]
- butorphanol, partial agonist at μ- and a pure agonist at κ-opioid receptor and antagonist activity at the delta opioid receptor (δ)[3]
- nalbuphine, κ-agonist/μ-antagonist analgesic[4]
Agonist–antagonist opioids usually have a ceiling effect – over particular dose they don't increase their potency.[5] Hence agonist–antagonist opioids have a lower addiction potential but also lower analgesic efficacy and are more likely to produce psychotomimetic effects.[6]
Agonist–antagonist opioids that block delta while activating mu opioid receptors produce analgesia without the development of tolerance.[7]
See also
References
- ↑ Hoskin PJ, Hanks GW (1991). "Opioid agonist-antagonist drugs in acute and chronic pain states". Drugs. 41 (3): 326–44. doi:10.2165/00003495-199141030-00002. PMID 1711441.
- ↑ Hollister LE (17 July 1991). "AMA Drug Evaluations Annual 1991". JAMA: The Journal of the American Medical Association. 266 (3): 97. doi:10.1001/jama.1991.03470030126039.
- ↑ Commiskey S, Fan LW, Ho IK, Rockhold RW (2005). "Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors". Journal of Pharmacological Sciences. 98 (2): 109–16. doi:10.1254/jphs.CRJ05001X. PMID 15942128.
- ↑ Schmidt WK, Tam SW, Shotzberger GS, Smith DH, Clark R, Vernier VG (1985). "Nalbuphine". Drug and Alcohol Dependence. 14 (3–4): 339–62. doi:10.1016/0376-8716(85)90066-3. PMID 2986929.
- ↑ Benson GJ, Tranquilli WJ (1992). "Advantages and guidelines for using opioid agonist-antagonist analgesics". Veterinary Clinics of North America: Small Animal Practice. 22 (2): 363–5. doi:10.1016/S0195-5616(92)50637-4. PMID 1585578.
- ↑ Lasagna L (1987). "Benefit-risk ratio of agonist-antagonist analgesics". Drug and Alcohol Dependence. 20 (4): 385–93. doi:10.1111/j.1360-0443.1989.tb00595.x. PMID 2894291.
- ↑ Dietis N, Guerrini R, Calo G, Salvadori S, Rowbotham DJ, Lambert DG (2009). "Simultaneous targeting of multiple opioid receptors: a strategy to improve side-effect profile". British Journal of Anaesthesia. 103 (1): 38–49. doi:10.1093/bja/aep129. PMID 19474215.