ArticleMolecular pain2016
Synthesis and characterization of a disubstituted piperazine derivative with T-type channel blocking action and analgesic properties.
Article in Molecular pain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 20 citations in OpenAlex.
- Synthesis and Biological Evaluation of Novel Benzhydrylpiperazine-Coupled Nitrobenzenesulfonamide Hybrids.ACS omega · 2021Article
- Synthesis and Modeling Studies of Furoxan Coupled Spiro-Isoquinolino Piperidine Derivatives as NO Releasing PDE 5 Inhibitors.Biomedicines · 2020Article
- Psychotropic Drugs for the Management of Chronic Pain and Itch.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Recent advances in the development of T-type calcium channel blockers for pain intervention.British journal of pharmacology · 2018Review
- Surfen is a broad-spectrum calcium channel inhibitor with analgesic properties in mouse models of acute and chronic inflammatory pain.Pflugers Archiv : European journal of physiology · 2017Article
- Novel Sulfamide-Containing Compounds as Selective Carbonic Anhydrase I Inhibitors.Molecules (Basel, Switzerland) · 2017Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundT-type calcium channels are important contributors to signaling in the primary afferent pain pathway and are thus important targets for the development of analgesics. It has been previously reported that certain piperazine-based compounds such as flunarizine are able to inhibit T-type calcium channels. Thus, we hypothesized that novel piperazine compounds could potentially act as analgesics.
resultsHere, we have created a series of 14 compound derivatives around a diphenyl methyl-piperazine core pharmacophore. Testing their effects on transiently expressed Cav3.2 calcium channels revealed one derivative (3-((4-(bis(4-fluorophenyl)methyl)piperazin-1-yl)methyl)-4-(2-methoxyphenyl)-1,2,5-oxadiazole 2-oxide, compound 10e) as a potent blocker. 10e mediate tonic block of these channels with an IC50 of around 4 micromolar. 10e also blocked Cav3.1 and Cav3.3 channels, but only weakly affected high-voltage-activated Cav1.2 and Cav2.2 channels. Intrathecal delivery of 10e mediated relief from formalin and complete Freund's adjuvant induced inflammatory pain that was ablated by genetic knockout of Cav3.2 channels.
conclusionsAltogether, our data identify a novel T-type calcium channel blocker with tight structure activity relationship (SAR) and relevant in vivo efficacy in inflammatory pain conditions.
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