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20-September-2008 09:55:57 - Inverse agonist Diagram showing effect of inverse agonist Diagram showing effect of inverse agonist In pharmacology, an inverse agonist is an agent which binds to the same receptor binding-site as an agonist for that receptor and reverses constitutive activity of receptors.1 Inverse agonists exert the opposite pharmacological effect of a receptor agonist. Inverse agonists are effective against certain types of receptors e.g. certain histamine receptors and GABA receptors2 which have intrinsic activity without the action of a ligand upon them also referred to as 'constitutive activity'. Receptor agonists, antagonists and inverse agonists bind to the same receptor types. The pharmacological effect of an inverse agonist is measured as the negative value of the agonist primarily due to the historical findings of the already known agonist. Therefore, if the agonist has a positive value and the inverse agonist has a negative value, the antagonist for the receptor takes both the agonist and inverse agonist back to a neutral state. One particular example is Ro15-4513 which is the inverse agonist of the benzodiazepine class of drugs such as alprazolam and diazepam. Ro15-4513 and the benzodiazepines both utilize the same GABA binding site on neurons, yet Ro15-4513 has the opposite effect, producing anxiety rather than the sedative effect of the benzodiazepines.3 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. ^ Sieghart W 1994. Pharmacology of benzodiazepine receptors: an update. J Psychiatry Neurosci 19 1: 24-9. PMID 8148363. See also Agonist Receptor antagonist 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. Retrieved on 2008-08-12. Retrieved from http://en..org/wiki/Inverse_agonist Categories: Pharmacology Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Français Polski Suomi 中文 This page was last modified on 18 August 2008, at 21:45
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