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  • compounds
  • The structure-activity relationships of these compounds have subsequently been investigated further leading to the development of a number of more potent analogues, derived by cyclisation around the indole or piperazine rings. (wikipedia.org)
  • Structurally it closely resembles cannabinoid compounds from patent WO 2003/035005 but with an indole core instead of indazole, and a simple pentyl chain on the indole 1-position. (wikipedia.org)
  • efficacy
  • It is selective for CB2, with Ki values of 0.64 nM at CB2 vs 270 nM at the psychoactive CB1 receptor, but while it exhibits selective analgesic, anti-inflammatory and anti-hyperalgesic effects at low doses, its high efficacy at both targets results in typical cannabis-like effects appearing at higher doses, despite its low binding affinity for CB1. (wikipedia.org)
  • Pharmacological
  • Pharmacological testing determined APICA to have an IC50 of 175 nM at CB1, only slightly less potent than JWH-018 which had an IC50 of 169 nM, but over four times more tightly binding than APINACA, which had an IC50 of 824 nM. (wikipedia.org)
  • The future of medical marijuana lies in classical pharmacological drug development, and indeed there has been a resurgence of scientific, as well as public, interest in the therapeutic applications of cannabinoids. (nap.edu)
  • Cannabis
  • Furthermore, APICA possesses cannabis-like effects in rats, and appears to be less potent than JWH-018 but more potent than THC. (wikipedia.org)
  • The cannabinoid molecules are derived from Cannabis sativa plant which acts on the cannabinoid receptors types 1 and 2 (CB 1 and CB 2 ) which have been explored as potential therapeutic targets for drug discovery and development. (hindawi.com)
  • Results of this study show that Δ 9 -THC and other cannabinoids exert antidepressant-like actions, and thus may contribute to the overall mood-elevating properties of cannabis. (pubmedcentralcanada.ca)
  • neurons
  • Conversely, cytokines/chemokines and their receptors that were first described in the immune system have been recently found in the brain, in glial cells, and neurons themselves. (frontiersin.org)
  • anandamide
  • The term cannabinoids is used in this chapter to refer to a group of substances that are structurally related to THC by virtue of a tricyclic chemical structure or that bind to cannabinoid receptors, such as the natural ligand anandamide. (nap.edu)
  • neuropathic
  • This makes LBP-1 peripherally selective, and while it was effective in animal models of neuropathic pain and allodynia, it did not produce cannabinoid-appropriate responding suggestive of central effects, at any dose tested. (wikipedia.org)
  • dopamine
  • As 2-NMC acts like a blocker for dopamine and norepinephrine, its possible to achive desirable results for researchers in laboratory conditions. (researchchemicalblog.com)
  • The endocannabinoids virodhamine and N -arachidonoyl dopamine are potent inhibitors of N -formyl- l -methionyl- l -leucyl- l -phenylalanine-induced migration of human neutrophils, with IC 50 values of 0.2 and 8.80 nM, respectively. (aspetjournals.org)
  • selectivity
  • Unfortunately, many of these drugs have numerous side effects, due to a lack of receptor subtype selectivity ( 4 ) and/or an interference with physiological signaling ( 5 ). (pubmedcentralcanada.ca)
  • Inhibitors
  • Human subjects injected with ghrelin remember pictures of food more clearly a day later and inhibitors of the ghrelin receptor could impair those memories [ 5 ]. (hindawi.com)
  • Patent
  • AM-679 AM-1235 AM-2201 AM-2232 AM-2233 FUBIMINA JWH-018 List of AM cannabinoids List of JWH cannabinoids THJ-2201 WO patent 200128557, Makriyannis A, Deng H, "Cannabimimetic indole derivatives", granted 2001-06-07 Willis PG, Katoch-Rouse R, Horti AG. (wikipedia.org)
  • known
  • Through the process of what is referred to as ''rational drug design,'' scientists manipulate the chemical structures of known cannabinoids to design better therapeutic agents. (nap.edu)
  • The transient receptor potential V2 (TRPV2) protein, also known as vanilloid receptor-like 1 (VRL-1), is a member of the TRP superfamily of nonselective, ligand-gated cation channels, many of which have been shown to serve as detectors and transducers of thermal sensory stimuli. (jneurosci.org)
  • Identification
  • Although this complexity has yet to be well elucidated, direct assessment of TRPV2 functions in vivo would be well served by the identification of TRPV2-selective agonist/antagonist and the generation of a mouse line lacking expression of TRPV2. (jneurosci.org)
  • whereas
  • 1 2 CB1 receptors are located in the central nervous system (CNS) as well as in the periphery, whereas CB2 receptors are mainly located in the peripheral tissues, such as immune cells. (arvojournals.org)
  • analgesic
  • It was developed with the aim of finding a water-soluble cannabinoid agonist suitable for intravenous use as an analgesic, but did not proceed to human trials, with the related compound Org 28611 chosen instead due to its better penetration into the brain. (wikipedia.org)
  • A-40174 (SP-1) is an analgesic drug which acts as a potent cannabinoid receptor agonist, and was developed by Abbott Laboratories in the 1970s. (wikipedia.org)
  • It was developed with the aim of finding a water-soluble cannabinoid agonist suitable for intravenous use as an analgesic, and while it achieved this aim and has progressed as far as Phase II clinical trials in humans as both a sedative and an analgesic, results against the comparison drugs (midazolam and morphine respectively) were not particularly favourable in initial testing. (wikipedia.org)
  • human
  • Several new cannabinoids are being developed for human use, but none has reached the stage of human testing in the United States. (nap.edu)
  • Inhibition
  • The activation of the CB 1 and CB 2 receptors causes the numerous intracellular effects which may be cell type and ligand specific and involve the inhibition of various voltage gated Ca +2 channels and adenylate cyclase activity and the activation of K + channels, resulting in lower levels of cAMP along with activation of MAPK pathways [ 5 ]. (hindawi.com)
  • brain
  • In addition, it has been recently evidenced that there are several cross-talks between the CXCL12/CXCR4-7 system and other neurotransmitter systems in the brain (such as GABA, glutamate, opioids, and cannabinoids). (frontiersin.org)
  • PPAR
  • FH535 is a compound that suppresses both Wnt/beta-catenin and peroxisome proliferator-activated receptor (PPAR) signaling. (medchemexpress.com)
  • The major group of regulators that is targeted is a group of nuclear hormone receptors known as peroxisome proliferator activated receptors (PPARα, δ, and γ). (wikipedia.org)
  • To become active and properly function as metabolic sensors and transcription regulators, the PPAR receptors must heterodimerize with another receptor known as the 9-cis retinoic acid receptor (RXR). (wikipedia.org)
  • The RXR receptor itself is the second major target of obesogens next to the PPAR receptors. (wikipedia.org)
  • The PPARα receptor, when complexed with RXR and activated by the binding of a lipid, promotes peroxisome proliferation leading to increased fatty acid β-oxidation. (wikipedia.org)
  • Substances, such a xenobiotics that target and act as agonists of PPARα, typically act to reduce overall serum concentrations of lipids. (wikipedia.org)
  • In contrast, the PPARγ receptor, when complexed with RXR and activated by the binding of fatty acids or their derivatives, promotes lipid biosynthesis and storage of lipids is favored over fatty acid oxidation. (wikipedia.org)
  • Substances that target and act as agonists of PPARγ/RXR complex typically act to increase overall serum concentrations of lipids. (wikipedia.org)
  • WIN55
  • 2001b) lately demonstrated that intracerebroventricular administration from the nonselective cannabinoid agonists HU210 or WIN55,212 to mice before an endotoxin problem attenuated proinflammatory cytokine creation and improved the degrees of the anti-inflammatory cytokine interleukin (IL)-10. (southpadremaps.com)
  • Also, the most common advancement of tolerance towards the severe hypothermic and cataleptic results noticed with cannabinoid agonists such as for example WIN55,212-2 is certainly avoided by repeated administration of L-NAME, a nonspecific NOS inhibitor (80). (achemmic.com)
  • For instance, the potent CB1 agonist CP-55,940 could decrease NO discharge in microglial cells activated with an endotoxin (82) and L-NAME elevated the central hypothermic aftereffect of the CB1 agonist WIN55,212-2 in rats (83). (achemmic.com)
  • signaling pathways
  • The Wnt signaling pathways are a group of signal transduction pathways made of proteins that pass signals from outside of a cell through cell surface receptors to the inside of the cell. (medchemexpress.com)
  • neuropathic pain
  • Recent clinical trials with smoked and vaporized marijuana, as well as other botanical extracts indicate the likelihood that the cannabinoids can be useful in the management of neuropathic pain, spasticity due to multiple sclerosis, and possibly other indications. (seattlepi.com)
  • cannabis
  • Recent advances in understanding of the mode of action of tetrahydrocannabinol and related cannabinoid in-gredients of marijuana, plus the` accumulating anecdotal reports on potential medical benefits have spurred increasing re-search into possible medicinal uses of cannabis. (seattlepi.com)
  • There are at least 113 different cannabinoids isolated from cannabis, exhibiting varied effects. (wikipedia.org)
  • CB2 receptors appear to be responsible for the anti-inflammatory and possibly other therapeutic effects of cannabis seen in animal models. (wikipedia.org)
  • At least 113 different cannabinoids have been isolated from the Cannabis plant To the right, the main classes of cannabinoids from Cannabis are shown. (wikipedia.org)
  • These cannabinoids produce the effects associated with cannabis by binding to the CB1 cannabinoid receptors in the brain. (wikipedia.org)
  • CBD shares a precursor with THC and is the main cannabinoid in CBD-dominant Cannabis strains. (wikipedia.org)
  • effects
  • Direct measurements of CB1- and CB2-particular effects have already been hindered from the lack of isotype-selective agonists. (southpadremaps.com)
  • The Ki values for binding central cannabinoid (CB1) and CB2 receptors are 9.0 and 2.94 nM, respectively, for a CB1:CB2 ratio of 3.06.1 Its effects on suppression of spontaneous activity, maximum possible antinociceptive effect in the tail-flick assay, and rectal temperature are comparable to those of WIN 55,212-2 when tested in rats. (fortunetelleroracle.com)
  • Numerous studies suggest that CBD acts to reduce the intoxicating effects of THC, such as memory impairment and paranoia. (meddaily.net)
  • Lipid signaling, broadly defined, refers to any biological signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. (wikipedia.org)
  • Its effects are produced by binding and acting as an agonist to the CB1 and CB2 cannabinoid receptors. (wikipedia.org)
  • These distinct effects are mediated primarily by CB1 cannabinoid receptors in the central nervous system, and CB2 cannabinoid receptors in the periphery. (wikipedia.org)
  • In humans it acts as a prodrug for γ-hydroxybutyric acid (GHB), and it is used as a recreational intoxicant with effects similar to alcohol. (wikipedia.org)
  • synthesis
  • L-Arginine is the nitrogen donor for synthesis of nitric oxide, a potent vasodilator that is deficient during times of sickle cell crisis. (medchemexpress.com)
  • inhibition
  • This impact is involved with some cannabinoid results such as for example AEA-induced inhibition of depolarization-evoked dopamine discharge in leech ganglia and arousal of neuropeptide discharge in the mammalian median eminence (77,79). (achemmic.com)
  • lymphocytes
  • The same results were found for certain inducers of apoptosis particularly stimulators of receptors in a class of lymphocytes (a type of white blood cell) called B-cells. (wikipedia.org)