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, whereas 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.
The efficacy of a full agonist is by definition 100%, a neutral antagonist has 0% efficacy, and an inverse agonist has < 0% (i.e., negative) efficacy.
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, whereas inverse agonists have anxiogenic (for example, Ro15-4513) or even convulsive effects (certain beta-carbolines).
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 binds melanocortin receptors 4 and 1 (Mc4R and Mc1R), respectively, with nanomolar affinities.
Affects one in three adults
Affecting about 35 percent of all adults in the United States according to the CDC, metabolic syndrome contributes to weight gain, by causing a state of internal starvation called metabolic starvation. This in turn leads to increases hunger, sugar cravings and increased portions leading to overeating and weight gain.
Cause and effect misunderstood
Since we traditionally thought that the portion control (which in turn was attributed wrongly to poor will power)is the cause of weight gain, rather than the effect of this metabolic starvation, all our traditional ideas about cause and effect of obesity were not only wrong but lead to the “blame the victim” attitude when it comes to obesity.
Secret of weight gain revealed
Secret of weight gain, and metabolic syndrome revealed - it has been recently proven that metabolic syndrome, and the weight gain itself are caused by a process called insulin resistance. Check your metabolic syndrome risk using the free Metabolic syndrome meter. Watch this amazing Ted Med video that reveals the secret of weight loss - Stop blaming the victim for obesity
- 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 2008-08-12.
- Inverse Agonists: An Illustrated Tutorial Panesar K, Guzman F. Pharmacology Corner. 2012