Pages in category "Kappa agonists"
The following 75 pages are in this category, out of 75 total, this list may not reflect recent changes (learn more).
The following 75 pages are in this category, out of 75 total, this list may not reflect recent changes (learn more).
1. Cebranopadol – As of November 2014, it is in phase III clinical trials. The ED50 values of 0. 5-5.6 µg/kg when introduced IV &25.1 µg/kg after oral administration, Cebranopadol shows highly potent and effective antinociceptive and antihypertensive effects in a variety of different animal models of pain. Notably, it has also found to be more potent in models of chronic neuropathic pain than acute nociceptive pain compared to selective μ-opioid receptor agonists. Relative to morphine, tolerance to the effects of cebranopadol has been found to be delayed. In addition, unlike morphine, cebranopadol has not been found to affect motor coordination or reduce respiration in animals at doses in or over the range for analgesia. As such, it may have improved and prolonged efficaciousness and greater tolerability in comparison to currently available opioid analgesics, etorphine Norbuprenorphine Mitragynine AT-076 About Cebranopadol - Oceanic Program Cebranopadol Search Results - ClinicalTrials. gov
2. CR665 – CR665, also known by the previous developmental code names FE-200665 and JNJ-38488502, is an all D-amino acid peptide that acts as a peripherally restricted κ-opioid receptor agonist. The selectivity for FE200665 is 1/16, 900/84,600 for the human κ, μ, the dose of FE200665 required to produce motor impairment was 548 times higher than the dose required for antinociceptive activity. It is being developed for use by Cara Therapeutics under the code name CR665, a small, double blind study was done in healthy humans to determine the analgesic effects. CR665 was dosed at 0.36 mg/kg I. V. and was compared to 15 mg oxycodone orally, CR665 had analgesic effects on visceral pain, but produced a hyperalgesic response in a skin pinch test
3. Cyclazocine – Cyclazocine is a mixed opioid agonist/antagonist related to dezocine, pentazocine and phenazocine. This family of drugs is called the benzomorphans or benzazocines. It is a KOR agonist and MOR partial agonist, and also has affinity for the DOR. Research into the use of cyclazocine for the treatment of patients with depression was undertaken by Fink. It showed that 8 out of 10 patients experienced moderate improvement, and MOR, although the side-effect threshold is often lower than the lowest effective dose
4. Diprenorphine – Diprenorphine, also known as diprenorfin, is a non-selective, high-affinity, weak partial agonist of the μ-, κ-, and δ-opioid receptor that is employed in veterinary medicine as an opioid antagonist. It is used to reverse the effects of super-potent opioid analgesics such as etorphine, the drug is not approved for use in humans. Diprenorphine is considered to be the specific reversing agent/antagonist for etorphine and carfentanil, since diprenorphine also has partial agonistic properties of its own, it should not be used on humans in the event that they are accidentally exposed to etorphine or carfentanil. Naloxone or naltrexone is the preferred human opioid receptor antagonist, because diprenorphine is a weak partial agonist of the opioid receptors rather than a silent antagonist, it can produce some opioid effects in the absence of other opioids at sufficient doses
5. Eluxadoline – It was approved for use in the United States in 2015. The drug originated from Janssen Pharmaceutica and was developed by Actavis, rare adverse effects, fatigue, bronchitis, viral gastroenteritis. Rare serious adverse effects include pancreatitis with an incidence of 0. 3% - higher incidence with 100 mg dose than with 75 mg dose. The risk is greater in those who do not have a gall bladder. Eluxadoline increases the concentrations of drugs which are OATP1B1 and BCRP substrates, also, coadministration of eluxadoline with rosuvastatin may increase the risk of rhabdomyolysis. Eluxadoline is a μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist that acts locally in the nervous system. In the in vitro studies, eluxadoline was found to be transported by OAT3, OATP1B1, however, it was not to be transported by OCT1 POU2F1, OAT1 Organic anion transporter 1, OCT2, OATP1B3, P-gp, or BCRP. Multidrug resistance-associated protein 2 -vesicular accumulation of eluxadoline was observed, indicating that the drug is a substrate of MRP2, also in the in vitro studies, it was observed that eluxadoline is an in vivo substrate of OATP1B1, OAT3, and MRP2. Finally, no inhibition or induction of cytochrome P450 enzymes was observed, following a 100 mg dose of eluxadoline, the Cmax was about 2 to 4 ng/ml and AUC was 12-22 ng. h/ml. Eluxadoline has linear pharmacokinetics with no accumulation upon repeated twice daily dosing, taking eluxadoline with high fat meal decreased the Cmax by 50% and AUC by 60%. The synthesis of eluxadoline was extensively discussed in the patent No, wO2006099060 A2, with the title, Process for the preparation of opioid modulators which was published in Sept.2006 Asimadoline Axelopran Difenoxin Diphenoxylate Loperamide
6. Enadoline – Enadoline is a drug which acts as a highly selective κ-opioid agonist. In human studies, it produced visual distortions and feelings of dissociation and it was studied as a potential analgesic, but abandoned because of the dose-limiting effects of dysphoria, which could be expected from a κ-opioid agonist. There was mention of its potential in treating comatose head injury or stroke victims, when enadoline was first reported in 1990, it was the most potent κ-selective analgesic ever reported. 25 times more potent than morphine and 17 times more potent than U-62066
7. Etorphine – Etorphine is a semi-synthetic opioid possessing an analgesic potency approximately 1, 000–3,000 times that of morphine. It was first prepared in 1960 from oripavine, which does not generally occur in opium poppy extract but rather the related plants Papaver orientale and it was later reproduced in 1963 by a research group at MacFarlan Smith in Gorgie, Edinburgh, led by Professor Kenneth Bentley. It can also be produced from thebaine, Etorphine is available legally only for veterinary use and is strictly governed by law. It is often used to immobilize elephants and other large mammals, diprenorphine, also known as Revivon, is an opioid receptor antagonist that can be administered in proportion to the amount of etorphine used to reverse its effects. Veterinary-strength etorphine is fatal to humans, for this reason the package as supplied to vets always includes the human antidote as well as etorphine. The LD50 in humans is 30 μg which led to the requirement that the medicine include an equal dose of an antidote, one of its main advantages is its speed of operation and, more importantly, the speed with which diprenorphine reverses the effects. The high incidence of side-effects, including severe depression, has caused etorphine to fall into disfavor in general veterinary practice. The high potency of etorphine means that sufficient etorphine can be administered to large mammals by projectile syringe. Large Animal Immobilon is a combination of etorphine plus acepromazine maleate, an etorphine antidote Large Animal Revivon contains mainly diprenorphine for animals and a human-specific naloxone-based antidote, which should be prepared prior to the etorphine. A 5–15 mg dose is enough to immobilize an African elephant, Etorphine is an extremely potent, non-selective full agonist of the μ-, δ-, and κ-opioid receptors. It also has relatively weak affinity for the nociceptin receptor, Etorphine has an LD50 of 30μg in humans. Its mu affinity is 0. 024nM compared with nalorphine nM0. 559Nm, diprenorphine Carfentanil has a Ki of 0.0000007. In Hong Kong, etorphine is regulated under Schedule 1 of Hong Kongs Chapter 134 Dangerous Drugs Ordinance and it can be used legally only by health professionals and for university research purposes. The substance can be given by pharmacists under a prescription, anyone who supplies the substance without prescription can be fined $10,000. The penalty for trafficking or manufacturing the substance is a $5,000,000 fine, possession of the substance for consumption without license from the Department of Health is illegal with a $1,000,000 fine and/or 7 years of jail time. In the Netherlands, etorphine is a list I drug of the Opium Law and it is used only for veterinary purposes in zoos to immobilize large animals. In the US, etorphine is listed as a Schedule I drug with an ACSCN of 9056, for both, the 2013 annual aggregate manufacturing quota for both was zero so presumably veterinary supplies of the hydrochloride are imported from Germany and/or the UK. In the UK, under the Misuse of Drugs Act 1971, etorphine is controlled as a Class A substance. com page on etorphine Etorphine, Molecule of the Month
8. 6'-Guanidinonaltrindole – 6-Guanidinonaltrindole is a κ−δ-opioid receptor selective ligand used in scientific research. With 6-GNTI, evidence was provided for the first time that receptor oligomizeration 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, 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
9. Hemorphin-4 – Hemorphin-4 is an endogenous opioid peptide of the hemorphin family which possesses antinociceptive properties and is derived from the β-chain of hemoglobin in the bloodstream. It is a tetrapeptide with the amino acid sequence Tyr-Pro-Trp-Thr and it acts as an agonist at these sites. Hemorphin-4 also has effects on angiotensin-converting enzyme, and as a result. Notably, inhibition of ACE also reduces enkephalin catabolism
10. Herkinorin – Herkinorin is an opioid analgesic that is an analogue of the natural product Salvinorin A. It was discovered in 2005 during structure-activity relationship studies into neoclerodane diterpenes, a study in primates showed it to act as both a peripherally active μ and κ agonist with a fast onset of action. The study did not find any evidence of activity in primates. Unlike most μ-opioid agonists, herkinorin does not promote the recruitment of β-arrestin-2 to the domain of the μ-opioid receptor, or induce receptor internalization. Kurkinorin Salvinorin B methoxymethyl ether RB-64
11. Ketazocine – Ketazocine, also known as ketocyclazocine, is a benzomorphan derivative used in opioid receptor research. Ketocyclazocine is an opioid that binds to the κ opioid receptor. Activation of this receptor is known to cause sleepiness, a decrease in pain sensation and dysphoria, paranoia and it also causes an increase in urine production because it inhibits the release of vasopressin. Unlike other opioids, substances that bind to the κ receptor theoretically do not depress the respiratory system
12. Lofentanil – Lofentanil is one of the most potent opioid analgesics known and is an analogue of fentanyl, which was developed in 1960. It is most similar to the potent opioid carfentanil, only slightly more potent. Lofentanil can be described as 3-methylcarfentanil, or 3-methyl-4-carbomethoxyfentanyl, while 3-methylfentanyl is considerably more potent than fentanyl itself, lofentanil is only slightly stronger than carfentanil. This suggests that substitution at both the 3 and 4 positions of the piperidine ring introduces steric hindrance which prevents μ-opioid affinity from increasing much further. As with other 3-substituted fentanyl derivatives such as ohmefentanyl, the stereoisomerism of lofentanil is very important, lofentanil is very similar to carfentanil in effects, but has a longer duration of action. Side effects of fentanyl analogs are similar to those of fentanyl itself, which include itching, nausea, and potentially serious respiratory depression, side effects from lofentanil might be particularly problematic given its reportedly long duration of action. In addition to acting on the receptor, lofentanil has also been found to act as a full agonist of the κ-opioid receptor
13. Matrine – Matrine is an alkaloid found in plants from the Sophora genus. It has a variety of effects, including anti-cancer effects. Matrine possesses strong antitumor activities in vitro and in vivo, inhibition of cell proliferation and induction of apoptosis are the likely mechanisms responsible for matrines antitumor activities. Matrine is a component of the traditional Chinese medical herb Sophora flavescens Ait, mu opioid agonism is associated with euphoria, while kappa opioid agonism is associated with dysphoria and psychotomimetic hallucinations. Both receptors are known to produce analgesia when activated, matrine and the related compound oxymatrine have an antifeedant effect against formosan subterranean termite
14. Menthol – Menthol is an organic compound made synthetically or obtained from corn mint, peppermint, or other mint oils. It is a waxy, crystalline substance, clear or white in color, the main form of menthol occurring in nature is -menthol, which is assigned the configuration. Menthol has local anesthetic and counterirritant qualities, and it is used to relieve minor throat irritation. Menthol also acts as a kappa opioid receptor agonist. Natural menthol exists as one pure stereoisomer, nearly always the form, the eight possible stereoisomers are, In the natural compound, the isopropyl group is in the trans orientation to both the methyl and hydroxyl groups. Thus, it can be drawn in any of the ways shown, The -, with the ring itself in a chair conformation, all three bulky groups can orient in equatorial positions. The two crystal forms for racemic menthol have melting points of 28 °C and 38 °C, pure -menthol has four crystal forms, of which the most stable is the α form, the familiar broad needles. Menthols ability to trigger the cold-sensitive TRPM8 receptors in the skin is responsible for the well-known cooling sensation it provokes when inhaled, eaten. In this sense, it is similar to capsaicin, the responsible for the spiciness of hot chilis. Menthols analgesic properties are mediated through an activation of κ-opioid receptors. Menthol also blocks sodium channels, reducing neural activity that may stimulate muscles. A study showed that absorption of ibuprofen is not increased by menthol. Some studies show that menthol acts as GABAA receptor positive allosteric modulator, Menthol also shares anaesthetic properties similar to propofol, by modulating same sites of GABAA receptor. Menthol is widely used in dental care as an antibacterial agent, effective against several types of streptococci. Mentha arvensis is the species of mint used to make natural menthol crystals. This species is grown in the Uttar Pradesh region in India. -Menthol occurs naturally in peppermint oil, obtained from Mentha x piperita, japanese menthol also contains a small percentage of the 1-epimer, -neomenthol. The biosynthesis of menthol has been investigated in M. x piperita and it begins with the synthesis of the terpene limonene, followed by hydroxylation, and then several reduction and isomerization steps
15. Metazocine – Metazocine is an opioid analgesic related to pentazocine. Metazocine is in Schedule II of the Controlled Substances Act 1970 of the United States as a Narcotic with ACSCN9240 with a 19 gram aggregate manufacturing quota as of 2014. The free base conversion ratio for salts includes 0.81 for the hydrochloride and 0.74 for the hydrobromide and it is listed under the Single Convention for the Control of Narcotic Substances 1961 and is controlled in most countries in the same fashion as is morphine. The prototype benzomorphan, metazocine, can be obtained from a variation of the morphinan synthesis, thus, reaction of the Grignard reagent from p-methoxybenzyl chloride with the lutidine methiodide affords the benzylated dihydropyridine. Reduction of the enamine π-bond leads to the tetrahydropyridine, cyclization by means of acid leads directly to the benzomorphan ring system. Demethylation of the ring system affords the phenol. Although this last compound is in fact a relatively potent analgesic, phenazocine Pentazocine Cyclazocine Org 6582, a functional MAT inhibitor that is otherwise analogous in structure to the parent compound of article
16. 18-Methoxycoronaridine – In animal studies it has proved to be effective at reducing self-administration of morphine, cocaine, methamphetamine, nicotine and sucrose. The sites of action in the include the medial habenula, interpeduncular nucleus, dorsolateral tegmentum. It has also shown to produce anorectic effects in obese rats. 18-MC is in the stages of human testing by Savant HWP. In 2002 the research team started trying to raise funds for human trials, national Institute on Drug Abuse gave a $6.5 million grant in 2012 to California-based drug developer company Savant HWP for the human trials. These compounds were found to act as selective α3β4 nicotinic acetylcholine antagonists. Glick, Ramirez, RL, Livi, JM, Maisonneuve, 18-Methoxycoronaridine acts in the medial habenula and/or interpeduncular nucleus to decrease morphine self-administration in rats
17. Mianserin – Mianserin is a psychoactive drug of the tetracyclic antidepressant therapeutic family. It is classified as a noradrenergic and specific serotonergic antidepressant and has antidepressant, anxiolytic, hypnotic, antiemetic, orexigenic and it is not approved for use in the US, but its analogue, mirtazapine, is. Mianserin was the first antidepressant to reach the UK market that was less dangerous than the tricyclic antidepressants in overdose, mianserin received TGA approval in May 1996. Similarly to its analogue, mirtazapine, mianserin has been tried as a strategy in treatment-resistant depression with some success. Mianserin has been tried, similarly to mirtazapine, as an adjunct in schizophrenia and has found to reduce negative and cognitive symptoms. Mianserin has demonstrated efficacy as a monotherapy for the treatment of Parkinsons disease psychosis in a clinical trial. Rare adverse effects include Oedema — the swelling of the bodys tissues due to fluid draining into said tissues, arthralgia Arthritis Rash Akathisia — a sense of inner restlessness that is often distressing for patients. Some cases of mianserin-induced blood dyscrasias have been fatal, gynaecomastia — abnormal breast enlargement in males. Pruritus — itchiness Hypertension Tachycardia Tinnitus — hearing ringing in the ears in the absence of an actual sound, conversely, CYP2D6 inducers would likely lead to reduced mianserin plasma concentrations and hence potentially diminish the therapeutic effects of mianserin. As a high affinity H1 receptor inverse agonist, mianserin has strong antihistamine effects, contrarily, it has negligible affinity for the mACh receptors, and thus lacks anticholinergic properties. It was recently found to be a weak κ-opioid receptor partial agonist, in addition, mianserin also appears to be a potent antagonist of the neuronal octopamine receptor. --Mianserin is approximately 200–300 times more active than its enantiomer --mianserin
18. Morphine – Morphine is a pain medication of the opiate type which is found naturally in a number of plants and animals. It acts directly on the nervous system to decrease the feeling of pain. It can be taken for both pain and chronic pain. Morphine is frequently used for pain from myocardial infarction and during labour and it can be given by mouth, by injection into a muscle, by injecting under the skin, intravenously, into the space around the spinal cord, or rectally. Maximum effect is around 20 min when given intravenously and 60 min when given by mouth while duration of effect is three and seven hours. Potentially serious side effects include a decreased respiratory effort and low blood pressure, morphine has a high potential for addiction and abuse. If the dose is reduced after long-term use, withdrawal may occur, common side effects include drowsiness, vomiting, and constipation. Caution is advised when used during pregnancy or breast feeding, as morphine will affect the baby, morphine was first isolated between 1803 and 1805 by Friedrich Sertürner. This is generally believed to be the first isolation of an ingredient from a plant. Merck began marketing it commercially in 1827, morphine was more widely used after the invention of the hypodermic syringe in 1853–1855. Sertürner originally named the substance morphium after the Greek god of dreams, the primary source of morphine is isolation from poppy straw of the opium poppy. In 2013, an estimated 523,000 kilograms of morphine were produced, about 45,000 kilograms were used directly for pain, an increase over the last twenty years of four times. Most use for this purpose was in the developed world, about 70% of morphine is used to make other opioids such as hydromorphone, oxycodone and heroin. It is a Schedule II drug in the United States, Class A in the United Kingdom and it is on the World Health Organizations List of Essential Medicines, the most effective and safe medicines needed in a health system. Morphine is sold under trade names. Morphine is used primarily to treat both acute and chronic severe pain and it is also used for pain due to myocardial infarction and for labor pains. Its duration of analgesia is about three to seven hours, however, concerns exist that morphine may increase mortality in the setting of non ST elevation myocardial infarction. Morphine has also traditionally used in the treatment of acute pulmonary edema
19. Nalfurafine – Nalfurafine is an antipruritic that is marketed in Japan for the treatment of uremic pruritus in individuals with chronic kidney disease undergoing hemodialysis. It acts as a potent, selective, centrally-penetrant κ-opioid receptor agonist and it has also been referred to as the first non-narcotic opioid drug in history. Nalfurafine was derived from modification of the opioid antagonist naltrexone. It was first synthesized and characterized in 1998, and was approved for use in Japan as an intravenous drug under the brand name Remitch in 2009. The developer of nalfurafine also sought approval in Europe under the brand name Winfuran, unlike other KOR agonists, nalfurafine does not produce hallucinogenic effects in humans. In rodents, a low dose of nalfurafine was found not to produce conditioned place preference or aversion, the most common side effect of low-dose nalfurafine seen in clinical trials was insomnia, with few other adverse effects observed. The drug also shows evidence of tolerance for effects such as analgesia. In animals, nalfurafine produces anti-scratch, antinociceptive, sedative, nalfurafine is an orally active, centrally acting, highly potent, selective full agonist of the κ-opioid receptor. As touched on above, nalfurafine shows atypical properties as a KOR agonist relative to other drugs, notably, it does not completely substitute for the prototypical KOR agonist U-50488 in rodents, indicating qualitative differences in the discriminative effects of the two compounds. Moreover, unlike U-50488, it produces neither conditioned place aversion or preference in rodents, the drug is a 4, 5-epoxymorphinan derivative, and is structurally unique relative to other KOR agonists. Nalfurafine may be a biased agonist of the KOR or a KOR subtype-selective agonist, as such, more research is needed to clarify the distinct mechanisms and effects of this drug. Nalfurafine has been found in vitro to bind to the receptor and to possess weak partial agonist activity at this site. However, in vivo, nalfurafine has shown no indications of MOR agonism or antagonism in animals or humans, including no evidence of rewarding or reinforcing effects or physical dependence. Nalfurafine has been found to be effective in a variety of animal models relevant to drug abuse, addiction, and dependence, asimadoline Butorphanol Difelikefalin Nalbuphine Nalmefene Naltriben Noribogaine RB-64 Salvinorin A