 | |
| Identifiers | |
|---|---|
| |
| PubChem CID | |
| ChemSpider | |
| Chemical and physical data | |
| Formula | C23H25BrN2O3 |
| Molar mass | 457.368 g·mol−1 |
| 3D model (JSmol) | |
| |
WIN 54,461 (6-Bromopravadoline) is a drug that acts as a potent and selective inverse agonist for the cannabinoid receptor CB2. [1]
WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) but has an entirely different chemical structure.
The cannabinoid receptor type 2, abbreviated as CB2, is a G protein-coupled receptor from the cannabinoid receptor family that in humans is encoded by the CNR2 gene. It is closely related to the cannabinoid receptor type 1 (CB1), which is largely responsible for the efficacy of endocannabinoid-mediated presynaptic-inhibition, the psychoactive properties of tetrahydrocannabinol (THC), the active agent in cannabis, and other phytocannabinoids (plant cannabinoids). The principal endogenous ligand for the CB2 receptor is 2-Arachidonoylglycerol (2-AG).
Originally synthesized by chemist Wayne E. Kenney, BAY 38-7271 (KN 38-7271) is a drug which is a cannabinoid receptor agonist developed by Bayer AG. It has analgesic and neuroprotective effects and is used in scientific research, with proposed uses in the treatment of traumatic brain injury. It is a full agonist with around the same potency as CP 55,940 in animal studies, and has fairly high affinity for both CB1 and CB2 receptors, with Ki values of 2.91nM at CB1 and 4.24nM at CB2. It has been licensed to KeyNeurotek Pharmaceuticals for clinical development, and was in Phase II trials in 2008 but its development appears to have stopped.
JWH-015 is a chemical from the naphthoylindole family that acts as a subtype-selective cannabinoid agonist. Its affinity for CB2 receptors is 13.8 nM, while its affinity for CB1 is 383 nM, meaning that it binds almost 28 times more strongly to CB2 than to CB1. However, it still displays some CB1 activity, and in some model systems can be very potent and efficacious at activating CB1 receptors, and therefore it is not as selective as newer drugs such as JWH-133. It has been shown to possess immunomodulatory effects, and CB2 agonists may be useful in the treatment of pain and inflammation. It was discovered and named after John W. Huffman.
JWH-030 is a research chemical which is a cannabinoid receptor agonist. It has analgesic effects and is used in scientific research. It is a partial agonist at CB1 receptors, with a Ki of 87 nM, making it roughly half the potency of THC. It was discovered and named after John W. Huffman.
JWH-051 is an analgesic drug which is a cannabinoid agonist. Its chemical structure is closely related to that of the potent cannabinoid agonist HU-210, with the only difference being the removal of the hydroxyl group at position 1 of the aromatic ring. It was discovered and named after John W. Huffman.
L-759,633 is an analgesic drug that is a cannabinoid agonist. It is a fairly selective agonist for the CB2 receptor, with selectivity of 163x for CB2 over CB1.
L-759,656 is an analgesic drug that is a cannabinoid agonist. It is a highly selective agonist for the CB2 receptor, with selectivity of 414x for CB2 over CB1, although it is still not as selective as newer agents such as HU-308.
O-823 is a drug which is a cannabinoid derivative that is used in scientific research. It is described as a mixed agonist/antagonist at the cannabinoid receptor CB1, meaning that it acts as an antagonist when co-administered alongside a more potent CB1 agonist, but exhibits weak partial agonist effects when administered by itself.
JTE-907 is a drug used in scientific research that acts as a selective CB2 inverse agonist. It has antiinflammatory effects in animal studies, thought to be mediated by an interaction between the CB2 receptor and IgE.
A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They include antagonists, inverse agonists, and antibodies of CBRs. The discovery of the endocannabinoid system led to the development of CB1 receptor antagonists. The first CBR inverse agonist, rimonabant, was described in 1994. Rimonabant blocks the CB1 receptor selectively and has been shown to decrease food intake and regulate body-weight gain. The prevalence of obesity worldwide is increasing dramatically and has a great impact on public health. The lack of efficient and well-tolerated drugs to cure obesity has led to an increased interest in research and development of CBR antagonists. Cannabidiol (CBD), a naturally occurring cannabinoid, is a non-competitive CB1/CB2 receptor antagonist. And Δ9-tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid, modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. CBD is a very low-affinity CB1 ligand, that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant.
GW-405,833 (L-768,242) is a drug that acts as a potent and selective partial agonist for the cannabinoid receptor subtype CB2, with an EC50 of 0.65 nM and selectivity of around 1200x for CB2 over CB1 receptors. Animal studies have shown it to possess antiinflammatory and anti-hyperalgesic effects at low doses, followed by ataxia and analgesic effects when the dose is increased. Selective CB2 agonist drugs such as GW-405,833 are hoped to be particularly useful in the treatment of allodynia and neuropathic pain for which current treatment options are often inadequate.
AM-630 (6-Iodopravadoline) is a drug that acts as a potent and selective inverse agonist for the cannabinoid receptor CB2, with a Ki of 32.1 nM at CB2 and 165x selectivity over CB1, at which it acted as a weak partial agonist. It is used in the study of CB2 mediated responses and has been used to investigate the possible role of CB2 receptors in the brain. AM-630 is significant as one of the first indole derived cannabinoid ligands substituted on the 6-position of the indole ring, a position that has subsequently been found to be important in determining affinity and efficacy at both the CB1 and CB2 receptors, and has led to the development of many related derivatives.
AM-2233 is a drug that acts as a highly potent full agonist for the cannabinoid receptors, with a Ki of 1.8 nM at CB1 and 2.2 nM at CB2 as the active (R) enantiomer. It was developed as a selective radioligand for the cannabinoid receptors and has been used as its 131I derivative for mapping the distribution of the CB1 receptor in the brain. AM-2233 was found to fully substitute for THC in rats, with a potency lower than that of JWH-018 but higher than WIN 55,212-2.
SR144528 is a drug that acts as a potent and highly selective CB2 receptor inverse agonist, with a Ki of 0.6 nM at CB2 and 400 nM at the related CB1 receptor. It is used in scientific research for investigating the function of the CB2 receptor, as well as for studying the effects of CB1 receptors in isolation, as few CB1 agonists that do not also show significant activity as CB2 agonists are available. It has also been found to be an inhibitor of sterol O-acyltransferase, an effect that appears to be independent from its action on CB2 receptors.
AZ-11713908 is a drug developed by AstraZeneca which is a peripherally selective cannabinoid agonist, acting as a potent agonist at the CB1 receptor and a partial agonist at CB2. It has poor blood–brain barrier penetration, and so while it is an effective analgesic in animal tests, it produces only peripheral effects at low doses, with much weaker symptoms of central effects compared to other cannabinoid drugs such as WIN 55,212-2. Many related benzimidazole-derived cannabinoid ligands are known.
MN-25 (UR-12) is a drug invented by Bristol-Myers Squibb, that acts as a reasonably selective agonist of peripheral cannabinoid receptors. It has moderate affinity for CB2 receptors with a Ki of 11 nM, but 22x lower affinity for the psychoactive CB1 receptors with a Ki of 245 nM. The indole 2-methyl derivative has the ratio of affinities reversed however, with a Ki of 8 nM at CB1 and 29 nM at CB2, which contrasts with the usual trend of 2-methyl derivatives having increased selectivity for CB2 (cf. JWH-018 vs JWH-007, JWH-081 vs JWH-098).
O-2050 is a drug that is a classical cannabinoid derivative, which acts as an antagonist for the CB1 receptor. This gives it an advantage in research over many commonly used cannabinoid antagonists, such as rimonabant, which at higher doses act as inverse agonists at CB1 as well as showing off-target effects. However, while O-2050 acts as a silent antagonist in vitro, some tests in vivo have suggested it may show agonist activity under certain circumstances.
Cannabinor (PRS-211,375) is a drug which acts as a potent and selective cannabinoid CB2 receptor agonist. It is classed as a "nonclassical" cannabinoid with a chemical structure similar to that of cannabidiol. It has a CB2 affinity of 17.4nM vs 5585nM at CB1, giving it over 300x selectivity for CB2. It showed analgesic effects in animal studies especially in models of neuropathic pain, but failed in Phase IIb human clinical trials due to lack of efficacy.
 | This cannabinoid related article is a stub. You can help Wikipedia by expanding it. |