Английская Википедия:Ganaxolone
Шаблон:Short description Шаблон:Refimprove science Шаблон:Use dmy dates Шаблон:Infobox drug
Ganaxolone, sold under the brand name Ztalmy, is a medication used to treat seizures in people with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder.[1][2] Ganaxolone is a neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator.[1]
The most common side effects of treatment with ganaxolone include somnolence (sleepiness), fever, excessive saliva or drooling, and seasonal allergy.[3]
Ganaxolone was approved for medical use in the United States in March 2022,[1][3] and in the European Union in July 2023.[4] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[5][6]
Medical uses
Ganaxolone is indicated for the treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder.[1][4]
Pharmacology
Mechanism of action
The exact mechanism of action for ganaxolone is unknown; however, results from animal studies suggest that it acts by blocking seizure propagation and elevating seizure thresholds.[7][8]
Ganaxolone is thought to modulate both synaptic and extrasynaptic GABAA receptors to normalize over-excited neurons.[2] Ganaxolone's activation of the extrasynaptic receptor is an additional mechanism that provides stabilizing effects that potentially differentiates it from other drugs that increase GABA signaling.[2]
Ganaxolone binds to allosteric sites of the GABAA receptor to modulate and open the chloride ion channel, resulting in a hyperpolarization of the neuron.[2] This causes an inhibitory effect on neurotransmission, reducing the chance of a successful action potential (depolarization) from occurring.[2][7][8]
It is unknown whether ganaxolone possesses significant hormonal activity in vivo, with a 2020 study finding evidence of in vitro binding to the membrane progesterone receptor.[9]
Chemistry
Ganaxolone is an analog of the neurosteroid allopregnanolone that possesses no known hormonal activity and, instead, is thought to primarily function by binding to GABAA receptors as a positive allosteric modulator.[10]
Other pregnane neurosteroids include alfadolone, alfaxolone, hydroxydione, minaxolone, pregnanolone (eltanolone), and renanolone, among others.[11]
History
The FDA approved ganaxolone based on evidence from a single, double-blind, randomized, placebo-controlled study (Study 1, NCT03572933) of 101 participants with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder who were two years of age and older.[3] The trial was conducted at 36 sites in 8 countries including Australia, France, Israel, Italy, Poland, Russian Federation, the United Kingdom, and the United States.[3] Forty-four (40.7%) of the participants were from US sites.[3] Safety was assessed from a pool of two clinical studies.[3] These include the study of participants with cyclin-dependent kinase-like 5 deficiency disorder and a clinical study that included seven additional participants from a trial of ganaxolone in children and young adults.[3]
References
External links
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- ↑ 1,0 1,1 1,2 1,3 Ошибка цитирования Неверный тег
<ref>; для сносокZtalmy FDA labelне указан текст - ↑ 2,0 2,1 2,2 2,3 2,4 Шаблон:Cite journal
- ↑ 3,0 3,1 3,2 3,3 3,4 3,5 3,6 Шаблон:Cite web Шаблон:PD-notice
- ↑ 4,0 4,1 Ошибка цитирования Неверный тег
<ref>; для сносокZtalmy EPARне указан текст - ↑ Шаблон:Cite web Шаблон:PD-notice
- ↑ Шаблон:Cite report Шаблон:PD-notice
- ↑ 7,0 7,1 Шаблон:Cite journal
- ↑ 8,0 8,1 Шаблон:Cite journal
- ↑ Шаблон:Cite journal
- ↑ Шаблон:Cite web
- ↑ Шаблон:Cite patent
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