Publicaties

The effects of phosphorothioate antisense oligodeoxynucleotides against exons-1, -2, -3 and -4 of the human mu-opioid receptor were studied in the CHO-mu-opioid receptor cells using aequorin luminescence-based calcium assay. All four antisense oligodeoxynucleotides significantly decreased the level of mu-opioid receptor mRNA in comparison with the non-treated cells, used as control. However, no statistically significant differences between ...

The mu opioid receptor (MOR) is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, ...

Abstract: A screening of conformationally constrained aromatic amino acids as base cores for the preparation of new NK1 receptor antagonists resulted in the discovery of three new NK1 receptor antagonists, 19 [Ac-Aba-Gly-NH-3',5'-(CF3)(2)-Bn] 20 [Ac-Aba-Gly-NMe-3',5'-(CF3)(2)-Bn], and 23 [Ac-Tic-NMe-3',5'-(CF3)(2)-Bn], which were able to counteract the agonist effect of substance P, the endogenous ligand of NK1R. The most active NK1 antagonist ...

A screening of conformationally constrained aromatic amino acids as base cores for the preparation of new NK1 receptor antagonists resulted in the discovery of three new NK1 receptor antagonists, 19 [Ac-Aba-Gly-NH-3',5'-(CF(3))(2)-Bn], 20 [Ac-Aba-Gly-NMe-3',5'-(CF(3))(2)-Bn], and 23 [Ac-Tic-NMe-3',5'-(CF(3))(2)-Bn], which were able to counteract the agonist effect of substance P, the endogenous ligand of NK1R. The most active NK1 antagonist of ...

New psychoactive substances (NPS) are introduced on the illicit drug market at a rapid pace. Their molecular targets are often inadequately elucidated, which contributes to the delayed characterization of their pharmacological effects. Inspired by earlier findings, this study set out to investigate the mu opioid receptor (MOR) activation potential of a large set of psychedelics, substances which typically activate the serotonin (5-HT2A) receptor ...

The Mu opioid receptor (MOR) has been the subject of intense research over the past decades, especially in the field of analgesic therapeutics. It is the primary target for both clinical and recreational opioids. Recently, camelid-derived nanobodies have received significant attention due to their applicability in stabilizing the crystal structure of activated MOR, via specific recognition of and binding to the active receptor conformation. In ...

The penetration of the blood–brain barrier (BBB) combined with the receptor-subtype selectivity determines the medical activity of opioid peptides within the central nervous system (CNS). The opioid receptor-subtype selectivity can be assessed not only by the classic radio-ligand binding methods, but also by novel techniques such as SAW (surface acoustic wave) measuring binding kinetics. Pharmacokinetics include metabolic stability, brain influx ...

Abstract: Novel dermorphin tetrapeptides are described in which Tyr(1) is replaced by Dmt(1), where D-Ala(2) and Gly(4) are N-methylated, and where Phe(3)-Gly(4) residue is substituted by the constrained Aba(3)-Gly(4) peptidomimetic. Most of these peptidic ligands displayed binding affinities in the nanomolar range for both mu- and delta-opioid receptors but no detectable affinity for the kappa-opioid receptor. Measurements of cAMP accumulation, ...

Mu-opioid analgesics are a mainstay in the treatment of acute and chronic pain of multiple origins, but their side effects, such as constipation, respiratory depression, and abuse liability, adversely affect patients. The recent demonstration of the up-regulation and membrane targeting of the delta-opioid receptor (DOR) following inflammation and the consequent enhanced therapeutic effect of delta-opioid agonists have enlivened the search for ...

The efficacy of naltrexone to treat alcohol use disorder (AUD) is modest. A better understanding of the neurobiology underlying naltrexone effects could optimize treatments. We evaluated the occupancy of the kappa opioid receptor (KOR) by naltrexone measured with [11C]-LY2795050 positron emission tomography (PET) as a predictor of response to naltrexone. Response to naltrexone was defined as the difference in craving and the difference between ...