To study drug-receptor interactions, new thio-derivatives of salvinorin A, an extremely potent natural kappa-opioid receptor (KOR) agonist, were synthesized. Obtained compounds were examined for receptor binding affinity. Analogs with the same configuration at carbon atom C-2 as in natural salvinorin A showed higher affinity to KOR than their corresponding epimers.

Opioid receptors and neurokinin 1 receptor (NK1R) are found highly expressed in the central nervous system. The co-localization of these two kinds of receptors suggests that they might interact with each other in both the transmission and modulation of the pain signal. In this review, we explore the relationships between opioid receptors and NK1R. Substance P (SP) plays a modulatory role in the...

κ Opioid receptor activation by traditional arylacetamide agonists and the novel neoclerodane diterpene κ opioid receptor agonist Salvinorin A (Sal A) results in attenuation of cocaine-seeking behavior in pre-clinical models of addiction. However, adverse effects such as sedation, depression and aversion limit their clinical utility. The Sal A analogue, 2-methoxy-methyl salvinorin B (MOM Sal B)...

The well characterized human breast cancer cell line, MCF-7, has been shown to possess membrane receptors for various opioid ligands, and these compounds have been shown to modulate the growth of the cells in culture. Using specific radioligands for the receptor types, we were able to demonstrate that the MCF-7 cells possess multiple opioid receptor types. Relatively high-affinity-binding sites...

Quaternary narcotic antagonists that are assumed not to penetrate the blood-brain barrier following systemic administration are commonly used to distinguish between peripheral and central actions of opiates. In mammals, these antagonists have a lower affinity for opioid receptors than their tertiary parent compounds. The relative affinity of quaternary vs. tertiary antagonists either for opioid...

A facile synthesis for novel loperamide analogs as potential μ opioid receptors is described. The synthetic procedure for compound 5, which contains two 4-phenyl piperidine scaffolds, was optimized, and this compound was synthesized in excellent yield. We also describe a mild and highly efficient protocol for the synthesis of compounds 6 and 7.

Benzomorphan core is a versatile structure. In fact, it represented the skeleton of drugs with different mechanism of action, from opioid to σ1 receptor, from antiviral to antiproliferative. Based upon these considerations, the design, synthesis and biological evaluation of benzomorphan-based compounds as putative antiviral and/or antitumoral drug candidates could represent a valid and versatil...

Opiates are still the most effective and widely used treatments for acute and chronic pain. However, the problems associated with morphine and other standard opioid analgesics severely limit their effectiveness in the clinic. PPL-101 and PPL-103 derived from morphine and morphinan ring systems contain a chiral N-substituent, which confers it with a unique combination of high-binding affinities ...

Opiates, one of the oldest known drugs, are the benchmark for treating pain. Regular opioid exposure also induces euphoria making these compounds addictive and often misused, as shown by the current epidemic of opioid abuse and overdose mortalities. In addition to the effect of opioids on their cognate receptors and signaling cascades, these compounds also induce multiple adaptations at cellula...

Development of opioid peptides as therapeutic agents has historically been limited due to pharmacokinetic issues including stability and blood-brain barrier (BBB) permeability. Glycosylation of opioid peptides can increase peptide serum stability and BBB penetration. To further define the requirements for optimizing in vivo antinociceptive potency following intravenous administration, we synthe...