ReviewThe international journal of neuropsychopharmacology2018
Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity.
Review in The international journal of neuropsychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Towards Explainable Computational Toxicology: Linking Antitargets to Rodent Acute Toxicity.Pharmaceutics · 2025Article
- Constitutive activity of the sweet taste receptor: Heavy water sweetness and beyond.Protein science : a publication of the Protein Society · 2025Review
- Influence of the neurotensin signaling system on feeding and satiety.Neuropharmacology · 2025Review
- Biased agonism in psychopharmacology: an opportunity to improve efficacy and safety of treatments.CNS spectrums · 2025Review
- Serotonin 2C receptors are also important in head-twitch responses in male mice.Psychopharmacology · 2025Article
- Identification of Orthosteric GABAACS omega · 2025Article
- Deciphering complexity of GPCR signaling and modulation: implications and perspectives for drug discovery.Clinical science (London, England : 1979) · 2025Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
Constitutive receptor activity/inverse agonism and functional selectivity/biased agonism are 2 concepts in contemporary pharmacology that have major implications for the use of drugs in medicine and research as well as for the processes of new drug development. Traditional receptor theory postulated that receptors in a population are quiescent unless activated by a ligand. Within this framework ligands could act as agonists with various degrees of intrinsic efficacy, or as antagonists with zero intrinsic efficacy. We now know that receptors can be active without an activating ligand and thus display "constitutive" activity. As a result, a new class of ligand was discovered that can reduce the constitutive activity of a receptor. These ligands produce the opposite effect of an agonist and are called inverse agonists. The second topic discussed is functional selectivity, also commonly referred to as biased agonism. Traditional receptor theory also posited that intrinsic efficacy is a single drug property independent of the system in which the drug acts. However, we now know that a drug, acting at a single receptor subtype, can have multiple intrinsic efficacies that differ depending on which of the multiple responses coupled to a receptor is measured. Thus, a drug can be simultaneously an agonist, an antagonist, and an inverse agonist acting at the same receptor. This means that drugs have an additional level of selectivity (signaling selectivity or "functional selectivity") beyond the traditional receptor selectivity. Both inverse agonism and functional selectivity need to be considered when drugs are used as medicines or as research tools.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.