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25-533: XLR-11 ( 5"-fluoro-UR-144 or 5F-UR-144 ) is a drug that acts as a potent agonist for the cannabinoid receptors CB 1 and CB 2 with EC 50 values of 98 nM and 83 nM, respectively. It is a 3-(tetramethylcyclopropylmethanoyl)indole derivative related to compounds such as UR-144 , A-796,260 and A-834,735 , but it is not specifically listed in the patent or scientific literature alongside these other similar compounds, and appears to have not previously been made by Abbott Laboratories , despite falling within

50-455: A distinction is now often made between efficacy and effectiveness . The word efficacy is used in pharmacology and medicine to refer both to the maximum response achievable from a pharmaceutical drug in research settings, and to the capacity for sufficient therapeutic effect or beneficial change in clinical settings. In pharmacology, efficacy ( E max ) is the maximum response achievable from an applied or dosed agent, for instance,

75-417: A magnesium ion unless the cell is also experiencing depolarization . These differences show that agonists have unique mechanisms of action depending on the receptor activated and the response needed. The goal and process remains generally consistent however, with the primary mechanism of action requiring the binding of the agonist and the subsequent changes in conformation to cause the desired response at

100-526: A biological response. A physiological agonist is a substance that creates the same bodily responses but does not bind to the same receptor. 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", or selective receptor modulators . As mentioned above, agonists have

125-406: A drug demonstrates a health benefit over a placebo or other intervention when tested in an ideal situation, such as a tightly controlled clinical trial." These studies focus on a primary parameter to be shown statistically different between placebo and intervention groups. Comparisons of this type are called 'explanatory' randomized controlled trials , whereas 'pragmatic' trials are used to establish

150-451: 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 (measured by the TD 50 , the dose that produces toxicity in 50% of individuals). This relationship, termed the therapeutic index , is defined as the ratio TD 50 : ED 50 . In general,

175-462: A drug will produce a biological effect, a property known as potency . In medicine, efficacy is the capacity for beneficial change (or therapeutic effect ) of a given intervention (for example a drug, medical device , surgical procedure , or a public health intervention). Establishment of the efficacy of an intervention is often done relative to other available interventions, with which it will be compared. Specifically, efficacy refers to "whether

200-678: A novel compound invented specifically for grey-market recreational use. XLR-11 was banned in New Zealand by being added to the temporary class drug schedule, as of 13 July 2012. The U.S. Drug Enforcement Administration (DEA) made XLR11 illegal under the Federal Controlled Substances act for the foreseeable future as of January 2024. It has also been banned in Florida as of 11 December 2012. Arizona banned XLR-11 on 3 April 2013. As of October 2015, XLR-11

225-483: A small molecule drug. Intrinsic activity is a relative term for a drug's efficacy relative to a drug with the highest observed efficacy. It is a purely descriptive term that has little or no mechanistic interpretation. In order for a drug to have an effect, it needs to bind to its target, and then to affect the function of this target. The target of a drug is commonly referred to as a receptor , but can in general be any chemically sensitive site on any molecule found in

250-742: Is a controlled substance in China. XLR-11 is banned in the Czech Republic. XLR-11 has been linked to hospitalizations due to its use. XLR-11 has been linked to acute kidney injury in some users, along with AM-2201 . Agonist From the Greek αγωνιστής (agōnistēs), contestant; champion; rival < αγων (agōn), contest, combat; exertion, struggle < αγω (agō), I lead, lead towards, conduct; drive Receptors can be activated by either endogenous agonists (such as hormones and neurotransmitters ) or exogenous agonists (such as drugs ), resulting in

275-429: Is by single ion channel analysis of ligand gated ion channels. It is still not possible to do this for G protein-linked receptors. In the case of the glycine receptor and the nicotinic acetylcholine receptor (muscle type), it has been proposed by Sivilotti et al . that opening of the ion channel involves two steps after agonist is bound. Firstly a conformation change to a higher affinity (but still shut) form, followed by

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300-492: Is not a dead letter, but rather, the power of the Holy Spirit is inherent in it and that Scripture does not compel a mere intellectual assent to its doctrine, resting on logical argumentation, but rather it creates the living agreement of faith . The Smalcald Articles affirm, "in those things which concern the spoken, outward Word , we must firmly hold that God grants His Spirit or grace to no one, except through or with

325-580: Is used to describe whether a pesticide is effective in controlling a pest or disease. In Protestant Theology (esp. in Lutheran but also in Calvinist doctrine) efficacy is an attribute of Scripture . The efficacy of Scripture means that it is united with the power of the Holy Spirit and with it, not only demands, but also creates the acceptance of its teaching and that this teaching produces faith and obedience . Efficacy further means that Holy Scripture

350-470: The effectiveness of an intervention regarding also non-specific parameters. Effectiveness refers to "how the drug works in a real-world situation", and is "often lower than efficacy because of interactions with other medications or health conditions of the patient, sufficient dose or duration of use not prescribed by the physician or followed by the patient, or use for an off-label condition that had not been tested." In agriculture and forestry, efficacy

375-428: The muscarinic acetylcholine receptor and NMDA receptor and their respective agonists. For the muscarinic acetylcholine receptor , which is a G protein-coupled receptor (GPCR), the endogenous agonist is acetylcholine . The binding of this neurotransmitter causes the conformational changes that propagate a signal into the cell. The conformational changes are the primary effect of the agonist, and are related to

400-514: The NMDA receptor requires both the endogenous agonists , N-methyl-D-aspartate (NMDA) and glycine . These co-agonists are both required to induce the conformational change needed for the NMDA receptor to allow flow through the ion channel , in this case calcium. An aspect demonstrated by the NMDA receptor is that the mechanism or response of agonists can be blocked by a variety of chemical and biological factors. NMDA receptors specifically are blocked by

425-415: The agonist's binding affinity and agonist efficacy . Other agonists that bind to this receptor will fall under one of the different categories of agonist mentioned above based on their specific binding affinity and efficacy. The NMDA receptor is an example of an alternate mechanism of action, as the NMDA receptor requires co-agonists for activation. Rather than simply requiring a single specific agonist,

450-482: The body. The nature of such binding can be quantified by characterising how tightly these molecules, the drug and its receptor, interact: this is known as the affinity . Efficacy, on the other hand, is a measure of the action of a drug once binding has occurred. The maximum response, E max , will be reduced if efficacy is sufficiently low. The definition of efficacy has been object for discussion. The only way in which absolute measures of efficacy have been obtained

475-480: The claims of patent WO 2006/069196. XLR-11 was found to produce rapid, short-lived hypothermic effects in rats at doses of 3 mg/kg and 10 mg/kg, suggesting that it is of comparable potency to APICA and STS-135 . A forensic standard for this compound is available, and a representative mass spectrum has been posted on Forendex. XLR-11 was instead first identified by laboratories in 2012 as an ingredient in synthetic cannabis smoking blends, and appears to be

500-455: The concentration of agonist needed to elicit half of the maximum biological response of the agonist. The EC 50 value is useful for comparing the potency of drugs with similar efficacies producing physiologically similar effects. The smaller the EC 50 value, the greater the potency of the agonist, the lower the concentration of drug that is required to elicit the maximum biological response. When

525-517: The conformation change from shut to open. It was found that partial agonism results from deficiency in the first step, and that the opening and shutting steps are essentially the same for both full and partial agonists. This has been confirmed and extended by Sine and colleagues (2009). The implication of this work is that efficacy has to be defined by at least two equilibrium constants (or, more generally, by four rate constants). The combined influences of affinity and efficacy determine how effectively

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550-462: The narrower this margin, the more likely it is that the drug will produce unwanted effects. The therapeutic index emphasizes the importance of the margin of safety, as distinct from the potency, in determining the usefulness of a drug. Efficacy Efficacy is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as effectiveness , and it has often been used synonymously, although in pharmacology

575-455: The potential to bind in different locations and in different ways depending on the type of agonist and the type of receptor. The process of binding is unique to the receptor-agonist relationship, but binding induces a conformational change and activates the receptor. This conformational change is often the result of small changes in charge or changes in protein folding when the agonist is bound. Two examples that demonstrate this process are

600-551: The preceding outward Word." The Formula of Concord teaches that when humans reject the calling of the Holy Spirit, it is not a result of the Word being less efficacious. Instead, contempt for the means of grace is the result of "the perverse will of man, which rejects or perverts the means and instrument of the Holy Ghost, which God offers him through the call , and resists the Holy Ghost, who wishes to be efficacious, and works through

625-403: The receptor. This response as discussed above can vary from allowing flow of ions to activating a GPCR and transmitting a signal into the cell . Potency is the amount of agonist needed to elicit a desired response. The potency of an agonist is inversely related to its half maximal effective concentration (EC 50 ) value. The EC 50 can be measured for a given agonist by determining

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