ArticleFrontiers in pharmacology2023
Antidepressant-like activity of a brain penetrant HCN channel inhibitor in mice.
Article in Frontiers in pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Increased Ih Current Is Associated with Reduced Hippocampal CA1 Excitability in a Mouse Model of Multiple Sclerosis.eNeuro · 2026Article
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Guanfacine and HCN channels: bridging neuroinflammation and prefrontal cortex function in autism spectrum disorder.Frontiers in molecular neuroscience · 2026Review
- Design and validation of novel brain-penetrant HCN channel inhibitors to ameliorate social stress-induced susceptible phenotype.Molecular psychiatry · 2025Article
- Downregulation of the HCN1 Channel Alleviates Anxiety- and Depression-Like Behaviors in Mice With Cerebral Ischemia-Reperfusion Injury by Suppressing the NLRP3 Inflammasome.Journal of the American Heart Association · 2025Article
- Hyperpolarization-activated cyclic nucleotide-gated channels and epilepsy: genetics, circuits, and treatments.Frontiers in neurology · 2025Review
- Inhibition of HCN1 currents by norquetiapine, an active metabolite of the atypical anti-psychotic drug quetiapine.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Changes in Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) channel function have been linked to depressive-like traits, making them potential drug targets. However, there is currently no peer-reviewed data supporting the use of a small molecule modulator of HCN channels in depression treatment. Org 34167, a benzisoxazole derivative, has been patented for the treatment of depression and progressed to Phase I trials. In the current study, we analysed the biophysical effects of Org 34167 on HCN channels in stably transfected human embryonic kidney 293 (HEK293) cells and mouse layer V neurons using patch-clamp electrophysiology, and we utilised three high-throughput screens for depressive-like behaviour to assess the activity of Org 34167 in mice. The impact of Org 34167 on locomotion and coordination were measured by performing rotarod and ledged beam tests. Org 34167 is a broad-spectrum inhibitor of HCN channels, slowing activation and causing a hyperpolarising shift in voltage-dependence of activation. It also reduced
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.