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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 but exerts the opposite pharmacological effect. Inverse agonists are effective against certain types of receptors (e.g. certain histamine receptors / GABA receptors) which have intrinsic activity without the acting 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 Xanax and Valium). 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.

• Pharmacology of benzodiazepine receptors: an update by W. Sieghart in Journal of Psychiatry & Neuroscience (1994) Volume 19, pages 24-29.
• "Ethanol potentiation of GABAergic transmission in cultured spinal cord neurons involves gamma-aminobutyric acidA-gated chloride channels" by A. K. Mehta and M. K. Ticku in The Journal of Pharmacology and Experimental Therapeutics (1988) Volume 246, pages 558-564. PMID 2457076

• Agonist
• Receptor antagonist

• Inverse Agonists for Medical Students by William B. Jeffries, Ph.D., Creighton University Department of Pharmacology