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Papers of the Week

Papers: 24 Jun 2023 - 30 Jun 2023

Basic Science

Animal Studies, In Vitro Studies, Pharmacology/Drug Development


2023 Jun 17





New Insights into the Opioid Analgesic Profile of -(-)–Normetazocine-derived Ligands.


Costanzo G, Turnaturi R, Parenti C, Spoto S, Piana S, Dichiara M, Zagni C, Galambos AR, Essmat N, Marrazzo A, Amata E, Al-Khrasani M, Pasquinucci L


In this work, we report on the in vitro and in vivo pharmacological properties of LP1 analogs to complete the series of structural modifications aimed to generate compounds with improved analgesia. To do that, the phenyl ring in the -substituent of our lead compound LP1 was replaced by an electron-rich or electron-deficient ring and linked through a propanamide or butyramide spacer at the basic nitrogen of the (-)—normetazocine skeleton. In radioligand binding assays, compounds and were found to display nanomolar binding affinity for the μ opioid receptor (MOR) (K = 5.96 ± 0.08 nM and 1.49 ± 0.24 nM, respectively). In the mouse vas deferens (MVD) assay, compound showed an antagonist effect against DAMGO ([D-Ala, N-MePhe, Gly-ol]-enkephalin), a highly selective MOR prototype agonist, whereas compound produced naloxone reversible effect at MOR. Moreover, compound , as potent as LP1 and DAMGO at MOR, was able to reduce thermal and inflammatory pain assessed by the mouse tail-flick test and rat paw pressure thresholds (PPTs) measured by a Randall-Selitto test.