A receptor modulator, or receptor ligand, is a general term for a substance, endogenous or exogenous, that binds to and regulates the activity of chemical

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

s. They are

ligand In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...

s that can act on different parts of receptors and regulate activity in a positive, negative, or neutral direction with varying degrees of efficacy. Categories of these modulators include receptor agonists and

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rece ...

s, as well as receptor

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

s, orthosteric modulators, and

allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a Receptor (biochemistry), receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allos ...

s, Examples of receptor modulators in modern medicine include CFTR modulators, selective androgen receptor modulators (SARMs), and muscarinic ACh receptor modulators. = General Description = Currently, receptor modulators are categorized in the Agonist, Partial Agonist, Selective Tissue Modulators, Antagonist, and Inverse Agonist categories in terms of the affect they cause. They are further divided into Orthosteric or Allosteric Modulators according to how they effect said result. Typically, a chemical acts in an agonist fashion whenever it instigates or else facilitates a particular reaction by binding to a particular receptor. In contract, a chemical acts as an antagonist whenever binding to a particular receptor blocks or inhibits a particular response. Between these endpoints exists a gradient defined by a number of variables. One example is Selective Tissue Modulators, which mean a given ligand can behave differently according to the tissue type it is in. As for orthosteric and allosteric modulation, this describes the manner in which the ligand binds to the receptor in question: if it binds directly to the prescribed binding site of a receptor, the ligand is orthosteric in this instance; if the ligand alters the receptor by interacting with it at any place other than a binding site, allosteric interaction occurred. Note that a drug’s categorization does not dictate how another drug of the same family could be categorized or whether the same drug may also function in another category. An example is found in medications used to treat opioid addiction, with methadone, buprenorphine,

naloxone Naloxone, sold under the brand names Narcan (4 mg) and Kloxxado (8 mg) among others, is a medication used to reverse or reduce the effects of opioids. It is commonly used to counter decreased breathing in opioid overdose. Effects begin within ...

, and naltrexone all in separate categories or in more than one simultaneously. In addition, depending on the cell type, the specific effect, whether agonist, antagonist, inverse agonist, etc., could have a unique specific effect. An example is seen in

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

, under “Receptor Agonists,” as it interacts with multiple different cell types as an agonist, but incites multiple and different responses in both.

Agonists

Receptor Agonists

A receptor agonist is a chemical that binds to a receptor with the end result of directly inducing a

conformational change In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors. A macromolecule is usually flexible and dynamic. Its shape can change in response to changes in its environment or oth ...

in the bound receptor and activating a downstream effect. Some common examples are opium derivates, such as

heroin Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...

and Toll-like receptor agonists. Heroin functions in this manner, along with other opioids, when bound to µ-opioid receptors. Opioids’ manner of action are both concentration- and receptor-dependent, which provides a key difference between agonists and partial agonists. Another example is

, which activates cell receptors to instigate

blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...

uptake.

Partial Agonists

Partial agonists An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

are any chemical that can bind to a receptor without eliciting the maximum downstream response as compared to the response from a full agonist. A given partial agonist’s affinity for a given receptor is also irrelevant to the consequent effect. An example is buprenorphine, a partial opioid receptor agonist used to treat opioid addictions by directly substituting for them without the same strength of effect.

Selective Receptor Modulators

Receptor Antagonists

is any given ligand that binds to a receptor in some way without causing any immediate or downstream response, essentially neutralizing the receptor until something with a stronger affinity removes the antagonist or the antagonist itself unbinds. Generally, antagonists can act one of two ways: 1) they can either block the receptors directly, preventing the usual ligand from binding, such as in the case of atropine when it blocks specific

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

receptors to provide important medical benefits. This is competitive antagonism, as they are competing for the same binding sites on the receptor. The other is by binding to a receptor in a site other than the designated receptor site, inducing a conformational change to prevent the usual ligand(s) from binding and activating a downstream cascade. A commonly-seen and used receptor antagonist is

, another opioid competitive antagonist typically used to treat opioid overdoses by blocking receptors outright. Further elaboration can be found in “Orthosteric v. Allosteric Modulators."

Inverse Agonists

Inverse agonists In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse ...

differ from regular agonists in that they effect receptors to which an regular agonist binds such that the bound receptors demonstrate reduced activity compared to when they are normally inactive. In other words, inverse antagonists limit the efficacy of the bound receptor in some way. This is noted to be beneficial in instances wherein expression of receptors or up-regulated receptor sensitivity could be detrimental, thus making suppression of response the best recourse. A handful of examples of inverse agonist use in therapy include

β-blockers Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack (secondary prevention). They are al ...

, antihistamines, ACP-103 to treat Parkinson’s disease,

hemopressin Hemopressin (Hp) is an alpha hemoglobin fragment with the sequence PVNFKFLSH, originally identified in extracts of rat brain using an enzyme capture technique. It binds cannabinoid receptors, acting as an inverse agonist at CB1 receptors. Longer ...

, drugs to treat

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...

, and more besides.

References

Pharmacodynamics Signal transduction {{pharmacology-stub