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BMS‐986122
BMS‐986122 is a selective positive allosteric modulator (PAM) of the μ-opioid receptor (MOR). MOR PAMs like BMS-986122 could be useful as novel analgesics with reduced side effects compared to conventional opioid analgesics. However, the potential specifically of BMS-986121 and BMS-986122 as pharmaceutical drugs may be restricted due to their complex synthesis. Mechanism of action BMS-986122 can enhance the affinity and efficacy of various orthosteric MOR agonists, including the endogenous opioid peptides, for the MOR. However, its effects are dependent on the ligand, and in the case of morphine, it enhances efficacy without affecting affinity. BMS‐986122 has no MOR agonist activity, is selective for the MOR, and lacks PAM activity at the δ-opioid receptor (DOR). However, it has been identified as a silent allosteric modulator (SAM) of the DOR and κ-opioid receptor (KOR). Animal studies The drug has analgesic effects in animals. In contrast to MOR agonists, BMS-98 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
μ-opioid Receptor
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 (letter), 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, Gi alpha subunit, inhibiting adenylate cyclase activity, lowering Cyclic adenosine monophosphate, cAMP levels. Structure The structure of the inactive μ-opioid receptor has been determined with the antagonists Beta-Funaltrexamine, β-FNA and alvimopan. Many structures of the active state are also available, with agonists including DAMGO, Β-Endorphin, β-endorphin, fentanyl and morphine. The structure with the agonist BU72 has the h ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ignavine
Ignavine is a naturally occurring diterpene alkaloid found in '' Aconiti tuber''. It has been reported to act as a μ-opioid receptor (MOR) positive allosteric modulator (PAM). The drug potentiated responses to the selective MOR agonist DAMGO at low concentrations but inhibited DAMGO at high concentrations. Ignavine alone has been found to produce analgesic effects in animals, but with a biphasic dose–response curve. Although described as a MOR PAM, other research suggests that ignavine is a ligand of the orthosteric site of the MOR and does not act as a PAM. Instead, it may be a MOR partial agonist. However, more research is necessary to clarify its MOR actions. Ignavine was first isolated by 1952 and its reported MOR PAM activity was first reported by 2016. See also * BMS‐986122 BMS‐986122 is a selective positive allosteric modulator (PAM) of the μ-opioid receptor (MOR). MOR PAMs like BMS-986122 could be useful as novel analgesics with reduced side effects compare ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
MS1 (drug)
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. The drug has been found to augment the affinity (pharmacology), affinity of the MOR agonist levomethadone ((''R'')-methadone) for the MOR by 7-fold ''in vitro'' and to potentiate activation of the MOR by levomethadone by 4-fold in a G protein assay. However, MS1 displays strong probe dependence, and while it potentiates the MOR agonists levomethadone and morphine, it had no effect on the affinity or potency (pharmacology), potency of the MOR agonists DAMGO or endomorphin-1. MS1 shows a preference for β-arrestin recruitment over G protein activation with endomorphin-1 exposure. The drug's actions are reportedly similar to those of BMS-986122, though its unclear if their mechanism of action, mechanisms of action are the same. MS1 shows potentiated analgesic effects with opioids in animals. It also did not worsen opioid wit ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BMS-986187
BMS-986187 is a positive allosteric modulator (PAM) of the δ-opioid receptor (DOR) and the κ-opioid receptor (KOR). The drug is highly potent as a DOR PAM, with an of 30nM. It has been found to increase the affinity of the endogenous peptide DOR agonist leu-enkephalin for the receptor by 32-fold. The drug has been found to act as a biased allosteric agonist of the DOR, activating G protein signaling ( = 301nM; Emax = 92%) but with little capacity to recruit β-arrestin ( = 579μM) (bias factor = 1787). Although a PAM, BMS-986187 is able to activate the DOR even in the absence of an orthosteric agonist, and as such, has been referred to as an "ago-PAM". Subsequent to its discovery, BMS-987187 was found to act as a potent KOR PAM as well. It is also a weak μ-opioid receptor (MOR) PAM ( = 3,000nM), but has 100-fold selectivity for potentiation of the DOR over the MOR. BMS-986187 has about 20- to 30-fold higher affinity for the conserved allosteric site on the DOR and KOR rel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
