Dual Piperidine-Based Histamine H3 and Sigma-1 Receptor Ligands in the Treatment of Nociceptive and Neuropathic Pain

Authors
Szczepańska K, Karcz T, Dichiara M, Mogilski S, Kalinowska-Tłuścik J, Pilarski B, Leniak A, Pietruś W, Podlewska S, et al


Lab
Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.

Journal
J Med Chem

Abstract
In search of new dual-acting histamine H3/sigma-1 receptor ligands, we designed a series of compounds structurally based on highly active in vivo ligands previously studied and described by our team. However, we kept in mind that within the previous series, a pair of closely related compounds, KSK67 and KSK68, differing only in the piperazine/piperidine moiety in the structural core showed a significantly different affinity at sigma-1 receptors (σ1Rs). Therefore, we first focused on an in-depth analysis of the protonation states of piperazine and piperidine derivatives in the studied compounds. In a series of 16 new ligands, mainly based on the piperidine core, we selected three lead structures (3, 7, and 12) for further biological evaluation. Compound 12 showed a broad spectrum of analgesic activity in both nociceptive and neuropathic pain models based on the novel molecular mechanism.

BIOSEB Instruments Used:
Electronic Von Frey - Wireless (BIO-EVF-WRS)

Publication request

Thank you for your interest in our product range and your request for this publication, which will be sent to you if the research team and the journal allow it. Our commercial team will contact you as soon as possible.