ArticleBritish journal of pharmacology2021
The T-type calcium channel antagonist, Z944, reduces spinal excitability and pain hypersensitivity.
Article in British journal of pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Bibliometric and visualized analysis of current advances and future directions in epilepsy: from molecular basis to therapy.Frontiers in neurology · 2025Pooled it
- Inhibition of CaV1.4 channels by CaV3 channel antagonists ML218 and Z944.The Journal of general physiology · 2026Article
- The Increased Activity of CaV3.2 Channels Contributes to Nociceptors' Hyperexcitability and Chronic Neuropathic Pain Following Spinal Cord Injury in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Processing and sectioning of organ donor spinal cord tissue for electrophysiology on acute human spinal cord slices.Brain communications · 2026Article
- Recent advances in the pharmacology of voltage-gated ion channels.Pharmacological reviews · 2025Review
- Reticular thalamic hyperexcitability drives autism spectrum disorder behaviors in the Cntnap2 model of autism.Science advances · 2025Article
- Therapeutic Potential of Calcium Channel Blockers in Neuropsychiatric, Endocrine and Pain Disorders.Cells · 2025Review
- Voltage-Gated Ion Channels in Neuropathic Pain Signaling.Life (Basel, Switzerland) · 2025Review
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Regulatory Action of Calcium and Calcium Channels in Pain Pathways.International journal of biological sciences · 2025Review
- CaThe journal of headache and pain · 2024Article
- Store-operated calcium entry mediates hyperalgesic responses during neuropathy.FEBS open bio · 2023Article
- Current Drug Development Overview: Targeting Voltage-Gated Calcium Channels for the Treatment of Pain.International journal of molecular sciences · 2023Review
- DNA Methylation Changes in Blood Cells of Fibromyalgia and Chronic Fatigue Syndrome Patients.Journal of pain research · 2023Article
- The Role of Voltage-Gated Calcium Channels in Basal Ganglia Neurodegenerative Disorders.Current neuropharmacology · 2023Review
- MEPIRAPIM-derived synthetic cannabinoids inhibit T-type calcium channels with divergent effects on seizures in rodent models of epilepsy.Frontiers in physiology · 2023Article
- T-type calcium channel modulation by hydrogen sulfide in neuropathic pain conditions.Frontiers in pharmacology · 2023Review
- Neuropathic pain; what we know and what we should do about it.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Central and peripheral contributions of T-type calcium channels in pain.Molecular brain · 2022Review
- Voltage-dependent CaPflugers Archiv : European journal of physiology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
background and purposeT-type voltage-gated calcium channels are an emerging therapeutic target for neurological disorders including epilepsy and pain. Inhibition of T-type channels reduces the excitability of peripheral nociceptive sensory neurons and reverses pain hypersensitivity in male rodent pain models. However, administration of peripherally restricted T-type antagonists failed to show efficacy in multiple clinical and preclinical pain trials, suggesting that inhibition of peripheral T-type channels alone may be insufficient for pain relief. EXPERIMENTAL APPROACH: We utilized the selective and CNS-penetrant T-type channel antagonist, Z944, in electrophysiological, calcium imaging and behavioural paradigms to determine its effect on lamina I neuron excitability and inflammatory pain behaviours. KEY
resultsVoltage-clamp recordings from lamina I spinal neurons of adult rats revealed that approximately 80% of neurons possess a low threshold T-type current, which was blocked by Z944. Due to this highly prevalent T-type current, Z944 potently blocked action-potential evoked somatic and dendritic calcium transients in lamina I neurons. Moreover, application of Z944 to spinal cord slices attenuated action potential firing rates in over half of laminae I/II neurons. Finally, we found that intraperitoneal injection of Z944 (1-10 mg·kg CONCLUSION AND IMPLICATIONS: T-type calcium channels critically shape the excitability of lamina I pain processing neurons and inhibition of these channels by the clinical stage antagonist Z944 potently reverses pain hypersensitivity across sexes.
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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.