Agonist: Wikis

  

Note: Many of our articles have direct quotes from sources you can cite, within the Wikipedia article! This article doesn't yet, but we're working on it! See more info or our list of citable articles.

Encyclopedia

From Wikipedia, the free encyclopedia

Agonists
Efficacy spectrum of receptor ligands.

An agonist is a drug that binds to a receptor of a cell and triggers a response by the cell. An agonist often mimics the action of a naturally occurring substance.

An agonist produces an action. An antagonist blocks an action of an agonist.

Contents

Types

Receptors can be activated or inactivated either by endogenous (such as hormones and neurotransmitters) or exogenous (such as drugs) agonists and antagonists, resulting in stimulating or inhibiting a biological response. A physiological agonist is a substance that creates the same bodily responses, but does not bind to the same receptor.

An endogenous agonist for a particular receptor is a compound naturally produced by the body which binds to and activates that receptor. For example, the endogenous agonist for serotonin receptors is serotonin, and the endogenous agonist for dopamine receptors is dopamine.[1]

Efficacy spectrum

A superagonist is a compound that is capable of producing a greater maximal response than the endogenous agonist for the target receptor, and thus has an efficacy of more than 100%. This does not necessarily mean that it is more potent than the endogenous agonist, but is rather a comparison of the maximum possible response that can be produced inside the cell following receptor binding.

Full agonists bind (have affinity for) and activate a receptor, displaying full efficacy at that receptor. One example of a drug that acts as a full agonist is isoproterenol which mimics the action of adrenaline at β adrenoreceptors. Another example is morphine, which mimics the actions of endorphins at μ-opioid receptors throughout the central nervous system.

Partial agonists (such as buspirone, aripiprazole, buprenorphine, or norclozapine) also bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. One study of benzodiazepine active sedative hypnotics found that partial agonists have just under half the strength of full agonists.[2] Partial agonists such as abecarnil have demonstrated a reduced rate and reduced severity of dependence and withdrawal syndromes.[3]

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. Inverse agonists exert the opposite pharmacological effect of a receptor agonist.

Mechanistic

A co-agonist works with other co-agonists to produce the desired effect together. NMDA receptor activation requires the binding of both of its glutamate and glycine co-agonists. An antagonist blocks a receptor from activation by agonists.

An irreversible agonist is a type of agonist that binds permanently to a receptor in such a manner that the receptor is permanently activated. It is distinct from a mere agonist in that the association of an agonist to a recepter is reversible, whereas the binding of an irreversible agonist to a receptor is, at least in theory, irreversible. This causes the compound to produce a brief burst of agonist activity, followed by desensitisation and internalisation of the receptor, which with long-term treatment produces an effect more like an antagonist.

Selective

A selective agonist is selective for one certain type of receptor. It can additionally be of any of the aforementioned types.

New findings that broaden the conventional definition of pharmacology demonstrate that ligands can concurrently behave as agonist and antagonists at the same receptor, depending on effector pathways or tissue type. Terms that describe this phenomenon are "functional selectivity", "protean agonism",[4][5] or selective receptor modulators.[6]

Activity

Potency

The potency of an agonist is inversely related to its EC50 value. The EC50 can be measured for a given agonist by determining the concentration of agonist needed to elicit half of the maximum biological response of the agonist. The EC50 value is useful for comparing the potency of drugs with similar efficacies producing physiologically similar effects. The smaller the EC50 value, the greater the potency of the agonist the lower the concentration of drug that is required to elicit the maximum biological response.

Therapeutic index

When a drug is used therapeutically, it is important to understand the margin of safety that exists between the dose needed for the desired effect and the dose that produces unwanted and possibly dangerous side effects. This relationship, termed the therapeutic index, is defined as the ratio LD50:ED50. In general, the narrower this margin, the more likely it is that the drug will produce unwanted effects. The therapeutic index has many limitations, notably the fact that LD50 cannot be measured in humans and, when measured in animals, is a poor guide to the likelihood of unwanted effects in humans. Nevertheless, the therapeutic index emphasizes the importance of the margin of safety, as distinct from the potency, in determining the usefulness of a drug.

Etymology

From the Greek αγωνιστής (agōnistēs), contestant; champion; rival < αγων (agōn), contest, combat; exertion, struggle < αγω (agō), I lead, lead towards, conduct; drive

See also

References

  1. ^ Goodman and Gilman's Manual of Pharmacology and Therapeutics. (11th edition, 2008). p14. ISBN 0071443436
  2. ^ Yakushiji T, Fukuda T, Oyama Y, Akaike N (November 1989). "Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones". Br. J. Pharmacol. 98 (3): 735–40. PMID 2574062.  
  3. ^ Löscher W, Hönack D (April 1992). "Withdrawal precipitation by benzodiazepine receptor antagonists in dogs chronically treated with diazepam or the novel anxiolytic and anticonvulsant beta-carboline abecarnil". Naunyn Schmiedebergs Arch. Pharmacol. 345 (4): 452–60. doi:10.1007/BF00176624. PMID 1352384.  
  4. ^ Kenakin T (March 2001). "Inverse, protean, and ligand-selective agonism: matters of receptor conformation". FASEB J. 15 (3): 598–611. doi:10.1096/fj.00-0438rev. PMID 11259378.  
  5. ^ Urban JD, Clarke WP, von Zastrow M, Nichols DE, Kobilka B, Weinstein H, Javitch JA, Roth BL, Christopoulos A, Sexton PM, Miller KJ, Spedding M, Mailman RB (January 2007). "Functional selectivity and classical concepts of quantitative pharmacology". J. Pharmacol. Exp. Ther. 320 (1): 1–13. doi:10.1124/jpet.106.104463. PMID 16803859.  
  6. ^ Smith CL, O'Malley BW (February 2004). "Coregulator function: a key to understanding tissue specificity of selective receptor modulators". Endocr. Rev. 25 (1): 45–71. PMID 14769827.  







Got something to say? Make a comment.
Your name
Your email address
Message