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6'-Guanidinonaltrindole
6′-Guanidinonaltrindole (6′-GNTI) is a κ– δ- opioid receptor selective ligand used in scientific research. With 6′-GNTI, evidence was provided for the first time that receptor oligomerization plays functional role in living organisms. 6′-GNTI is an extremely biased agonist of the κ-opioid receptor. It is a potent partial agonist of the G protein pathway but does not recruit the β-arrestin pathway. Due to its functional selectivity for the G protein pathway, 6′-GNTI functions as an antagonist of nonbiased KOR agonists on the β-arrestin pathway. It is thought that 6′-GTNI may be able to produce analgesia without dysphoria and with a lower incidence of tolerance. See also * 5′-Guanidinonaltrindole * RB-64 * Noribogaine * ICI-199,441 ICI-199,441 is a drug which acts as a potent and selective κ-opioid agonist, and has analgesic effects. It is a biased agonist of the KOR, and is one of a relatively few KOR ligands that is G protein-biased rather than ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
κ-opioid Receptor
The κ-opioid receptor or kappa opioid receptor, abbreviated KOR or KOP, is a G protein-coupled receptor that in humans is encoded by the ''OPRK1'' gene. The KOR is coupled to the G protein Gi/G0 and is one of four related receptors that bind opioid-like compounds in the brain and are responsible for mediating the effects of these compounds. These effects include altering nociception, consciousness, motor control, and mood. Dysregulation of this receptor system has been implicated in alcohol and drug addiction. The KOR is a type of opioid receptor that binds the opioid peptide dynorphin as the primary endogenous ligand (substrate naturally occurring in the body). In addition to dynorphin, a variety of natural alkaloids, terpenes and synthetic ligands bind to the receptor. The KOR may provide a natural addiction control mechanism, and therefore, drugs that target this receptor may have therapeutic potential in the treatment of addiction. There is evidence that distribution ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Noribogaine
Noribogaine (actually O-desmethylibogaine), or 12-hydroxyibogamine, is the principal psychoactive metabolite of the oneirogen ibogaine. It is thought to be involved in the antiaddictive effects of ibogaine-containing plant extracts, such as ''Tabernanthe iboga''. Pharmacology Noribogaine is a potent serotonin reuptake inhibitor, but does not affect the reuptake of dopamine. Unlike ibogaine, noribogaine does not bind to the sigma-2 receptor. Similarly to ibogaine, noribogaine acts as a weak NMDA receptor antagonist and binds to opioid receptors. It has greater affinity for each of the opioid receptors than does ibogaine. Noribogaine is a hERG inhibitor and appears at least as potent as ibogaine. The inhibition of the hERG potassium channel delays the repolarization of cardiac action potentials, resulting in QT interval prolongation and, subsequently, in arrhythmias and sudden cardiac arrest. κ-Opioid receptor Noribogaine has been determined to act as a biased agonist of th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
5'-Guanidinonaltrindole
5'-Guanidinonaltrindole (5'-GNTI) is an opioid antagonist used in scientific research which is highly selective for the κ opioid receptor. It is 5x more potent and 500 times more selective than the commonly used κ-opioid antagonist norbinaltorphimine. It has a slow onset and long duration of action, and produces antidepressant effects in animal studies. It also increases allodynia by interfering with the action of the κ-opioid peptide dynorphin. In addition to activity at the KOR, 5'-GNTI has been found to act as a positive allosteric modulator of the α1A-adrenergic receptor ( EC50 = 41 nM), and this may contribute to its "severe transient effects". See also * 6'-Guanidinonaltrindole * Binaltorphimine * JDTic JDTic is a selective, long-acting ("inactivating") antagonist of the κ-opioid receptor (KOR). JDTic is a 4-phenylpiperidine derivative, distantly related structurally to analgesics such as pethidine and ketobemidone, and more closely to the ... Ref ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Drug Tolerance
Drug tolerance or drug insensitivity is a pharmacological concept describing subjects' reduced reaction to a drug following its repeated use. Increasing its dosage may re-amplify the drug's effects; however, this may accelerate tolerance, further reducing the drug's effects. Drug tolerance is indicative of drug use but is not necessarily associated with drug dependence or addiction. The process of tolerance development is reversible (e.g., through a drug holiday) and can involve both physiological factors and psychological factors. One may also develop drug tolerance to side effects, in which case tolerance is a desirable characteristic. A medical intervention that has an objective to increase tolerance (e.g., allergen immunotherapy, in which one is exposed to larger and larger amounts of allergen to decrease one's allergic reactions) is called drug desensitization. The opposite concept to drug tolerance is drug reverse tolerance (or drug sensitization), in which case the sub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Guanidines
Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experiencing renal failure. A guanidine moiety also appears in larger organic molecules, including on the side chain of arginine. Structure Guanidine can be thought of as a nitrogenous analogue of carbonic acid. That is, the C=O group in carbonic acid is replaced by a C=NH group, and each OH is replaced by a group. Isobutene can be seen as the carbon analogue in much the same way. A detailed crystallographic analysis of guanidine was elucidated 148 years after its first synthesis, despite the simplicity of the molecule. In 2013, the positions of the hydrogen atoms and their displacement parameters were accurately determined using single-crystal neutron diffraction. Production Guanidine can be obtained from natural sources, being first isolat ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Semisynthetic Opioids
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use disorder, reversing opioid overdose, and suppressing cough. Extremely potent opioids such as carfentanil are approved only for veterinary use. Opioids are also frequently used non-medically for their euphoric effects or to prevent withdrawal. Opioids can cause death and have been used for executions in the United States. Side effects of opioids may include itchiness, sedation, nausea, respiratory depression, constipation, and euphoria. Long-term use can cause tolerance, meaning that increased doses are required to achieve the same effect, and physical dependence, meaning that abruptly discontinuing the drug leads to unpleasant withdrawal symptoms. The euphoria attracts recreational use, and frequent, escalating recreational use of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ICI-199,441
ICI-199,441 is a drug which acts as a potent and selective κ-opioid agonist, and has analgesic effects. It is a biased agonist of the KOR, and is one of a relatively few KOR ligands that is G protein-biased rather than β-arrestin-biased. See also *U-47700 *U-50488 *U-69,593 U-69,593 is a drug which acts as a potent and selective κ1-opioid receptor agonist. In animal studies it has been shown to produce antinociception, anti-inflammation, anxiolysis (at low doses), respiratory depression, and diuresis, while ... References Acetamides Biased ligands Chloroarenes Kappa-opioid receptor agonists Pyrrolidines Synthetic opioids {{analgesic-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
RB-64
RB-64 (22-thiocyanatosalvinorin A) is a semi-synthetic salvinorin A, salvinorin derivative and a κ-opioid receptor (KOR) agonist which is used in scientific research. Its most remarkable property is its functional selectivity for G protein versus Arrestin beta 2, β-arrestin-2. RB-64 has a functional selectivity#bias factor, bias factor of 96 and is analgesic with fewer of the side-effects associated with unbiased KOR agonists. The analgesia-like effect is long-lasting. Compared with unbiased agonists, RB-64 evokes considerably less Receptor-mediated endocytosis, receptor internalization. See also * Herkinorin * Salvinorin B methoxymethyl ether * Salvinorin A * Nalfurafine References Further reading * * Synthetic opioids Kappa-opioid receptor agonists Kappa-opioid receptor antagonists Thiocyanates Biased ligands {{Organic-compound-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dysphoria
Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation. In psychiatry Intense states of distress and unease increase the risk of suicide, as well as being unpleasant in themselves. Relieving dysphoria is therefore a priority of psychiatric treatment. One may treat underlying causes such as depression or bipolar disorder as well as the dysphoric symptoms themselves. The ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM-5) categorizes specific dysphoria in the obsessive–compulsive spectrum. Dissatisfaction with being able-bodied can be diagnosed as body integrity dysphoria in the ICD-11. Gender dysphoria Gender dysphoria is discomfort, unhappiness or distress due to one's assigned sex. The current edition (DSM-5) of the ''Diagnostic and Statistical Manual of Mental Disorders'' uses the term "gender dysphoria" where it previ ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
