dc.contributor.author | Catalani, Valeria | |
dc.contributor.author | Botha, Michelle | |
dc.contributor.author | Corkery, John Martin | |
dc.contributor.author | Guirguis, Amira | |
dc.contributor.author | Vento, Alessandro | |
dc.contributor.author | Schifano, Fabrizio | |
dc.date.accessioned | 2022-12-15T11:05:08Z | |
dc.date.available | 2022-12-15T11:05:08Z | |
dc.date.issued | 2022-09-22 | |
dc.identifier.citation | Catalani , V , Botha , M , Corkery , J M , Guirguis , A , Vento , A & Schifano , F 2022 , ' Designer Benzodiazepines’ Activity on Opioid Receptors: A Docking Study ' , Current Pharmaceutical Design , vol. 28 , no. 32 , pp. 2639-2652 . https://doi.org/10.2174/1381612828666220510153319 | |
dc.identifier.issn | 1381-6128 | |
dc.identifier.other | ORCID: /0000-0001-8255-0660/work/124844251 | |
dc.identifier.uri | http://hdl.handle.net/2299/25953 | |
dc.description | © 2022 Bentham Science Publishers. This is the accepted manuscript version of an article which has been published in final form at https://doi.org/10.2174/1381612828666220510153319 | |
dc.description.abstract | BACKGROUND: Previous studies have reported that benzodiazepines (BZDs) seem to enhance euphoric and reinforcing properties of opioids in opioid users so that a direct effect on opioid receptors has been postulated, together with a possible synergistic induction of severe side effects due to co use of BDZs and opioids. This is particularly worrisome given the appearance on the market of designer benzodiazepines (DBZDs), whose activity/toxicity profiles are scarcely known. OBJECTIVES: This study aimed to evaluate, through computational studies, the binding affinity (or lack thereof) of 101 DBZDs identified online on the kappa, mu, and delta opioid receptors (K, M, DOR); and to assess whether their mechanism of action could include activation of the latter. METHODS: MOE® was used for the computational studies. Pharmacophore mapping based on strong opioids agonist binders' 3D chemical features was used to filter the DBZDs. Resultant DBZDs were docked into the crystallised 3D active conformation of KOR (PDB6B73), DOR (PDB6PT3) and MOR (PDB5C1M). Co-crystallised ligands and four strong agonists were used as reference compounds. A score (S, Kcal/mol) representative of the predicted binding affinity, and a description of ligand interactions were obtained from MOE®.RESULTS: The docking results, filtered for S < -8.0 and the interaction with the Asp residue, identified five DBZDs as putative binders of the three ORs : ciclotizolam, fluloprazolam, JQ1, Ro 48-6791, and Ro 48-8684.CONCLUSION: It may be inferred that at least some DBZDs may have the potential to activate opioid receptors. This could mediate/increase their anxiolytic, analgesic, and addiction potentials, as well as worsen the side effects associated with opioid co-use. | en |
dc.format.extent | 14 | |
dc.format.extent | 983265 | |
dc.language.iso | eng | |
dc.relation.ispartof | Current Pharmaceutical Design | |
dc.subject | Designer benzodiazepines | |
dc.subject | docking | |
dc.subject | Kappa-delta-mu opioid receptors | |
dc.subject | MOE® | |
dc.subject | NPSfinder® | |
dc.subject | pharmacophore mapping | |
dc.subject | Humans | |
dc.subject | Analgesics, Opioid/adverse effects | |
dc.subject | Receptors, Opioid/agonists | |
dc.subject | Designer Drugs/adverse effects | |
dc.subject | Receptors, Opioid, delta/agonists | |
dc.subject | Analgesics | |
dc.subject | Receptors, Opioid, mu/agonists | |
dc.subject | Ligands | |
dc.subject | Anti-Anxiety Agents | |
dc.subject | Benzodiazepines/adverse effects | |
dc.subject | Receptors, Opioid, kappa/agonists | |
dc.subject | Drug Discovery | |
dc.subject | Pharmacology | |
dc.title | Designer Benzodiazepines’ Activity on Opioid Receptors: A Docking Study | en |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Department of Pharmacy, Pharmacology and Postgraduate Medicine | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Unit | |
dc.contributor.institution | Centre for Health Services and Clinical Research | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.description.status | Peer reviewed | |
dc.date.embargoedUntil | 2023-09-22 | |
dc.identifier.url | http://www.scopus.com/inward/record.url?scp=85137343947&partnerID=8YFLogxK | |
rioxxterms.versionofrecord | 10.2174/1381612828666220510153319 | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |