Chemistry:XEN1101
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| Other names | encukalner, azetukalner |
| Routes of administration | By mouth |
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| Formula | C23H29FN2O |
| Molar mass | 368.496 g·mol−1 |
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XEN1101 (encukalner) is an experimental small molecule anticonvulsant and selective Kv7.2/Kv7.3 potassium channel opener being investigated as a treatment for refractory focal onset seizures[1][2][3][4][5] and major depressive disorder.[5]
Mechanism of action
XEN1101 works by selectively opening the KCNQ2/3 (Kv7.2/Kv7.3) voltage-gated potassium channels via positive allosteric modulation. The opening of these voltage-gated potassium channels, which are critical regulators of neuronal excitability, leads to an increase in the flow of potassium ions out of neurons, resulting in the neurons becoming hyperpolarized. This hyperpolarized resting state reduces the ability of the neuron to fire, thereby decreasing the likelihood of seizures.[2][3][5]
This mechanism of action shares similarities with the medication retigabine, which was withdrawn from the market in 2017 due to its link to skin pigmentation and retinitis pigmentosa.[1][5][6] XEN1101 has a different structure and does not appear to cause this effect or the development of the chromophoric phenazinium-type dimers that resulted in this side effect in retigabine.[1]
References
- ↑ 1.0 1.1 1.2 "Epilepsy: expert opinion on emerging drugs in phase 2/3 clinical trials". Expert Opinion on Emerging Drugs 27 (1): 75–90. March 2022. doi:10.1080/14728214.2022.2059464. PMID 35341431.
- ↑ 2.0 2.1 "TMS as a pharmacodynamic indicator of cortical activity of a novel anti-epileptic drug, XEN1101". Annals of Clinical and Translational Neurology 6 (11): 2164–2174. November 2019. doi:10.1002/acn3.50896. PMID 31568714. "XEN1101 is a novel positive allosteric modulator (“opener”) of the potassium channel KCNQ2/3 (Kv7.2/7.3) currently being developed by Xenon Pharmaceuticals Inc. for the treatment of focal epilepsy. Potentiating the open state of KCNQ2/3 channels favors a hyperpolarized resting state. This mechanism has been clinically proven effective for focal onset seizures using the KCNQ2/3 opener, retigabine.".
- ↑ 3.0 3.1 Ciccone, Isabella (10 October 2023). "Potassium Channel Opener XEN1101 Offers Simplicity and Strong Efficacy in Seizure Control". https://www.neurologylive.com/view/potassium-channel-opener-xen1101-offers-simplicity-strong-efficacy-seizure-control. "XEN1101 (Xenon Pharmaceuticals), part of a class of chemicals called potassium-channel openers, is an investigational antiseizure medication in development for patients with focal epilepsy. This treatment is designed to avert seizures by boosting the flow of potassium out of nerves and stopping them from firing."
- ↑ "Efficacy and Safety of XEN1101, a Novel Potassium Channel Opener, in Adults With Focal Epilepsy: A Phase 2b Randomized Clinical Trial". JAMA Neurology 80 (11): 1145–1154. October 2023. doi:10.1001/jamaneurol.2023.3542. PMID 37812429.
- ↑ 5.0 5.1 5.2 5.3 "The Potential of KCNQ Potassium Channel Openers as Novel Antidepressants". CNS Drugs 36 (3): 207–216. March 2022. doi:10.1007/s40263-021-00885-y. PMID 35258812.
- ↑ Hackethal, Veronica (15 June 2017). "Anticonvulsant Potiga Discontinued in June 2017". https://www.neurologylive.com/view/anticonvulsant-potiga-discontinued-june-2017.
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