Inverse agonist
In the field of pharmacology, an inverse agonist is an agent that binds to the same receptor as an agonist but induces a pharmacological response opposite to that agonist.
A prerequisite for an inverse agonist response is that the receptor must have a constitutive (also known as intrinsic or basal) level activity in the absence of any ligand. An agonist increases the activity of a receptor above its basal level while an inverse agonist decreases the activity below the basal level. A neutral antagonist has no activity in the absence of an agonist or inverse agonist but can block the activity of either.[1]
The efficacy of a full agonist is by definition 100%, a neutral antagonist, 0%, while an inverse agonist has < 0% (i.e., negative) efficacy.
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[edit] Examples
An example of a receptor that possesses basal activity and for which inverse agonists have been identified is the GABAA receptor. Agonists for the GABAA receptor (such as the benzodiazepines alprazolam and diazepam) elicit a sedative effect while inverse agonists have anxiogenic (for example, Ro15-4513) or even convulsive effects (certain beta-carbolines).[2][3]
Two known endogenous inverse agonists are the agouti related peptide (AgRP) and its associated peptide Agouti signaling peptide (ASIP) both are expressed in humans and each bind melanocortin receptors 4 and 1 (Mc4R and Mc1R) respectively with nanomolar affinities.[4]
[edit] References
- ^ Kenakin T (2004). "Principles: receptor theory in pharmacology". Trends Pharmacol. Sci. 25 (4): 186–92. doi:10.1016/j.tips.2004.02.012. PMID 15063082.
- ^ Mehta AK, Ticku MK (1988). "Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acidA-gated chloride channels". J. Pharmacol. Exp. Ther. 246 (2): 558–64. PMID 2457076. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2457076.
- ^ Sieghart W (1994). "Pharmacology of benzodiazepine receptors: an update". J Psychiatry Neurosci 19 (1): 24–9. PMC 1188559. PMID 8148363. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1188559.
- ^ Ollmann MM, Lamoreux ML, Wilson BD, Barsh GS (February 1998). "Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo". Genes Dev. 12 (3): 316–30. PMC 316484. PMID 9450927. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316484.
[edit] See also
[edit] External links
- Jeffries WB (1999-02-17). "Inverse Agonists for Medical Students". Office of Medical Education - Courses - IDC 105 Principles of Pharmacology. Creighton University School of Medicine - Department of Pharmacology. https://medicine.creighton.edu/courses/pharm/Dr.Jeffries/Inverse.asp. Retrieved 2008-08-12.
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