μ-Opioid receptors are among the most studied G protein-coupled receptors because of the therapeutic value of agonists, such as morphine, that are used to treat chronic pain. However, these drugs have significant side effects, such as respiratory suppression, constipation, allodynia, tolerance, and dependence, as well as abuse potential. Efforts to fine tune pain control while alleviating the s...

Extracts of four species of seaweeds, Ulva lactuca L. (green), Liagora farinosa Lamouroux (red), Padina pavonia L. and Turbinaria ornata Turn (brown), were screened for their antimicrobial, and antimalarial activities, and binding affinity for human opioid receptors. Phytochemical analysis led to the isolation and identification of 10 constituents: fucosterol, stearic acid, palmitic acid, palmi...

Opium and its derivatives are potent analgesics that also have many other pharmacological effects in the nervous system. These agents and the endogenous opioid peptides exert their effects by interacting with high-affinity receptors. Complementary DNAs encoding the delta, kappa and mu opioid receptors have been isolated and characterized. These receptors, which are members of the superfamily of...

JDTic analogues 4-15 which have the hydroxyl groups replaced with other groups were synthesized and their in vitro efficacy at the μ, δ, and κ opioid receptors determined and compared to JDTic using [(35)S]GTPγS assays. Compounds 4, 5, 6, 13, 14, and 15 had Ke = 0.024, 0.01, 0.039, 0.02, 0.11, and 0.041 nM compared to the Ke = 0.02 nM for JDTic at the κ receptor and were highly selective for th...

Pain is an unpleasant sensation that originates from ongoing or impending tissue damage. Management of different types of pain (acute, postoperative, inflammatory, neuropathic cancer) is challenging and yet the most frequent issue encountered by clinicians. Pharmacological therapy is the first line of approach for the treatment of pain and opioid drugs are prescribed for acute and chronic pain ...

In present study, some 4-piperidinopiperidine (PP) and 4-amino methylpiperidine (AMP) derivatives (PP1-3 and AMP4-9) have been synthesized to explore their analgesic potential. Activity of compounds evaluated by in-vivo thermal (tail immersion) method produced significant analgesia at different doses. Docking results explained good binding affinity of synthesized derivatives and potential inter...

Mitragynine (MG) and its major metabolites 7-hydroxymitragynine (7-OH-MG) are two of the major components of the plant extract Kratom, which is a tree planted in Southeast Asia. Kratom has long been used by opioid-dependent individuals as an alternative to their unavailable opioid of choice and chronic pain medication, as a stealth-to-urine drug screening opiate substitute while in opioid recov...

New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest ag...

The μ-opioid receptor (MOR) is the primary target for opioid analgesics. MOR induces analgesia through the inhibition of second messenger pathways and the modulation of ion channels activity. Nevertheless, cellular excitation has also been demonstrated, and proposed to mediate reduction of therapeutic efficacy and opioid-induced hyperalgesia upon prolonged exposure to opioids. In this mini-pers...

The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, is a potent κ-opioid receptor agonist, making it an attractive scaffold for development into a treatment for substance abuse. Although several successful semisynthetic studies have been performed to elucidate structure-activity relationships, the lack of analogues with substitutions to the furan ring of salvinorin...