Biomedicine: Move over, morphine

Systematic review: human gut dysbiosis induced by non‐antibiotic prescription medications

“…Morphine is often the drug of choice in cases of moderate or severe pain . However, previous works demonstrated that opioid drugs enable bacterial translocation by means of gut barrier disruption …”

Comparative pharmacology and toxicology of tramadol and tapentadol

“…The use, misuse and abuse of analgesics have increased throughout the last decades (Compton and Volkow, ; Manchikanti et al., ; Compton et al., ; Kaye et al., ). Prescription opioids, the mainstay of chronic pain treatment, have largely contributed to this phenomenon, leading to the so‐called opioid epidemic and a public health crisis associated with an increase in the number of opioid‐related morbidity and mortality (Burgess and Williams, ; Manchikanti et al., ; Mercadante et al., ; Meneghini et al., ; Compton et al., ; Mercadante, ; Crow, ; Just et al., ; Agarwal et al., ; Han et al., ; Pezalla et al., ). Besides the typical unwanted side effects caused by opioids, including bowel dysfunction and constipation, vomiting, nausea, itching, sex hormone dysfunction (hypogonadism), somnolence, sleep and concentration difficulties (which sometimes lead to treatment discontinuation), other effects related to tolerance, dependence and addiction potential, as well as possible fatal overdose, represent additional troubling concerns (Burgess and Williams, ; Manchikanti et al., ; Mercadante et al., , ; Gunther et al., ; Ventura et al., ).…”

“…Besides the typical unwanted side effects caused by opioids, including bowel dysfunction and constipation, vomiting, nausea, itching, sex hormone dysfunction (hypogonadism), somnolence, sleep and concentration difficulties (which sometimes lead to treatment discontinuation), other effects related to tolerance, dependence and addiction potential, as well as possible fatal overdose, represent additional troubling concerns (Burgess and Williams, ; Manchikanti et al., ; Mercadante et al., , ; Gunther et al., ; Ventura et al., ). Therefore, the demand for the development of new analgesic formulations with nonexistent or reduced side effects and abuse potential has never been so urgent (Burgess and Williams, ; Crow, ; Gunther et al., ; Pezalla et al., ; Vadivelu et al., ).…”

Opioid Receptor Activity and Analgesic Potency of DPDPE Peptide Analogues Containing a Xylene Bridge

“…3 Thus, it is highly desirable the design of "unbalanced" dual-acting opioid drugs as full δ-opioid receptor agonist and only as partial agonist of the μ-opioid receptor, which is strongly related to the development of tolerance and physical dependence. 4 Met-Enkephalin and Leu-enkephalin are linear endogenous pentapeptides with high affinity for DOP regulating human nociception; numerous structural modifications have been explored during the last years to investigate the structure− activity relationships (SAR) and to improve their selectivity; 5,6 H-Tyr-c[D-Pen-Gly-Phe-D-Pen]-OH (DPDPE) is the first synthetic prototype of highly selective constrained cyclic peptide for this receptor (Figure 1). 7 DPDPE is employed as radiolabeled δ receptor full agonist in the opioid binding assays due to its resistance to proteolytic degradation and permeability to the blood−brain barrier (BBB).…”