Mitragyna speciosa is a tropical evergreen tree of the Rubiaceae family native to Southeast Asia. It is indigenous to Cambodia, Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea, where its leaves, known as "kratom" have been used in herbal medicine since at least the 19th century. They have also historically been consumed via chewing, smoking, and as a tea. Kratom has opioid-like properties and some stimulant-like effects. As of 2018, the efficacy and safety of kratom are unclear. In 2019, the United States Food and Drug Administration (FDA) stated that there is no evidence that kratom is safe or effective for treating any condition. Some people take it for managing chronic pain, for treating opioid withdrawal symptoms, or for recreational purposes. The onset of effects typically begins within five to ten minutes and lasts for two to five hours.
The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ(mu)-opioid peptide (MOP) receptors. The prototypical μ-opioid receptor agonist is morphine, the primary psychoactive alkaloid in opium and for which the receptor was named, with mu being the first letter of Morpheus, the compound's namesake in the original Greek. It is an inhibitory G-protein coupled receptor that activates the Gi alpha subunit, inhibiting adenylate cyclase activity, lowering cAMP levels.
The δ-opioid receptor, also known as delta opioid receptor or simply delta receptor, abbreviated DOR or DOP, is an inhibitory 7-transmembrane G-protein coupled receptor coupled to the G protein Gi/G0 and has enkephalins as its endogenous ligands. The regions of the brain where the δ-opioid receptor is largely expressed vary from species model to species model. In humans, the δ-opioid receptor is most heavily expressed in the basal ganglia and neocortical regions of the brain.
Desmetramadol, also known as O-desmethyltramadol (O-DSMT), is an opioid analgesic and the main active metabolite of tramadol. Tramadol is demethylated by the liver enzyme CYP2D6 to desmetramadol in the same way as codeine, and so similarly to the variation in effects seen with codeine, individuals who have a less active form of CYP2D6 will tend to have reduced analgesic effects from tramadol. Because desmetramadol itself does not need to be metabolized to induce an analgesic effect, it can be used in individuals with CYP2D6 inactivating mutations.
7-Hydroxymitragynine (7-OH) is a terpenoid indole alkaloid from the plant Mitragyna speciosa, commonly known as kratom. It was first described in 1994 and is a human metabolite metabolized from mitragynine present in the Mitragyna speciosa, commonly known as kratom. 7-OH binds to opioid receptors like mitragynine, but research suggests that 7-OH binds with greater efficacy.
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, the family of chemical compounds of which salvinorin A is a member.
SNC-80 is an opioid analgesic compound that selectively activates μ–δ opioid receptor heteromers and is used primarily in scientific research. Discovered in 1994, SNC-80 was a pioneering non-peptide compound regarded as a highly selective agonist for the δ-opioid receptor.
Aeruginascin, also known as 4-phosphoryloxy-N,N,N-trimethyltryptamine (4-PO-TMT), is an indoleamine derivative which occurs naturally within the mushrooms Inocybe aeruginascens, Pholiotina cyanopus, and Psilocybe cubensis.
Rhynchophylline is an alkaloid found in certain Uncaria species (Rubiaceae), notably Uncaria rhynchophylla and Uncaria tomentosa. It also occurs in the leaves of Mitragyna speciosa (kratom) and Mitragyna tubulosa, a tree native to Thailand. Chemically, it is related to the alkaloid mitragynine.
An opioidergic agent is a chemical which directly or indirectly modulate the function of opioid receptors. Opioidergics comprise opioids, as well as allosteric modulators and enzyme affecting agents like enkephalinase inhibitors.
MT-45 (IC-6) is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co. It is chemically a 1-substituted-4-(1,2-diphenylethyl) piperazine derivative, which is structurally unrelated to most other opioid drugs. Racemic MT-45 has around 80% the potency of morphine, with almost all opioid activity residing in the (S) enantiomer. It has been used as a lead compound from which a large family of potent opioid drugs have been developed, including full agonists, partial agonists, and antagonists at the three main opioid receptor subtypes. Fluorinated derivatives of MT-45 such as 2F-MT-45 are significantly more potent as μ-opioid receptor agonists, and one of its main metabolites 1,2-diphenylethylpiperazine also blocks NMDA receptors.
IBNtxA, or 3-iodobenzoyl naltrexamine, is an atypical opioid analgesic drug derived from naltrexone. In animal studies it produces potent analgesic effects that are blocked by levallorphan and so appear to be μ-opioid mediated, but it fails to produce constipation or respiratory depression, and is neither rewarding or aversive in conditioned place preference protocols. These unusual properties are thought to result from agonist action at a splice variant or heterodimer of the μ-opioid receptor, rather than at the classical full length form targeted by conventional opioid drugs.
Cebranopadol is an opioid analgesic of the benzenoid class which is currently under development internationally by Grünenthal, a German pharmaceutical company, and its partner Depomed, a pharmaceutical company in the United States, for the treatment of a variety of different acute and chronic pain states. As of November 2014, it is in phase III clinical trials.
Iboga-type alkaloids are a set of monoterpene indole alkaloids comprising naturally occurring compounds found in Tabernanthe and Tabernaemontana, as well as synthetic structural analogs. Naturally occurring iboga-type alkaloids include ibogamine, ibogaine, tabernanthine, and other substituted ibogamines. Many iboga-type alkaloids display biological activities such as cardiac toxicity and psychoactive effects, and some have been studied as potential treatments for drug addiction.
Mitragynine is an indole-based alkaloid and is one of the main psychoactive constituents in the Southeast Asian plant Mitragyna speciosa, commonly known as kratom. It is an opioid that is typically consumed as a part of kratom for its pain-relieving and euphoric effects. It has also been researched for its use to potentially manage symptoms of opioid withdrawal.
HS665 is a drug which acts as a potent and selective κ-opioid receptor agonist, and has analgesic effects in animal studies. HS665 is not an agonist for the mu receptor, leading to less potential for abuse.
Speciociliatine is a major alkaloid of the plant Mitragyna speciosa, commonly known as kratom. It is a stereoisomer of Mitragynine and constitutes 0.00156 - 2.9% of the dried leaf material.
Collybolide is a secondary metabolite of the Rhodocollybia maculata mushroom, a basidiomycete fungus that grows on rotting conifer wood. It was previously believed to be a potent and selective kappa-opioid receptor agonist. However, a total synthesis and independent biological assay determined that collybolide neither excites nor suppresses kappa-opioid receptor signaling. Collybolide is unlikely to be psychoactive, although it has been shown to inhibit L-type calcium channels in isolated rat aorta.
BMS‐986122 is a selective positive allosteric modulator (PAM) of the μ-opioid receptor (MOR).
MS1 is a positive allosteric modulator (PAM) of the μ-opioid receptor (MOR). It was developed from structural modification of the earlier MOR PAM BMS‐986122.
