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| Trade names | Ztalmy |
| Other names | GNX; CCD-1042; 3β-Methyl-5α-pregnan-3α-ol-20-one; 3α-Hydroxy-3β-methyl-5α-pregnan-20-one |
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| Routes of administration | By mouth |
| Drug class | Neurosteroid |
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| ECHA InfoCard | 100.210.937 |
| Chemical and physical data | |
| Formula | C22H36O2 |
| Molar mass | 332.528 g·mol−1 |
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Ganaxolone, sold under the brand nameZtalmy, is amedication used to treatseizures in people withcyclin-dependent kinase-like 5 (CDKL5) deficiency disorder.[1][3] Ganaxolone is a neuroactive steroidgamma-aminobutyric acid (GABA) A receptor positive modulator.[1]
The most common side effects of treatment with ganaxolone includesomnolence (sleepiness), fever, excessive saliva or drooling, and seasonal allergy.[4]
Ganaxolone was approved for medical use in the United States in March 2022,[1][4][5] and in the European Union in July 2023.[2] The USFood and Drug Administration (FDA) considers it to be afirst-in-class medication.[6][7]
Ganaxolone is indicated for the treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder.[1][2][8][9]
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.[10][11]
Ganaxolone is thought to modulate bothsynaptic and extrasynapticGABAA receptors to normalize over-excitedneurons.[3] Ganaxolone's activation of the extrasynaptic receptor is an additional mechanism that provides stabilizing effects that potentially differentiates it from other drugs that increaseGABA signaling.[3]
Ganaxolone binds toallosteric sites of the GABAA receptor to modulate and open thechloride ion channel, resulting in ahyperpolarization of the neuron.[3] This causes an inhibitory effect onneurotransmission, reducing the chance of a successfulaction potential (depolarization) from occurring.[3][10][11]
It is unknown whether ganaxolone possesses significant hormonal activityin vivo, with a 2020 study finding evidence ofin vitro binding to the membraneprogesterone receptor.[12]
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Ganaxolone is ananalog of theneurosteroidallopregnanolone that possesses no known hormonal activity and, instead, is thought to primarily function by binding to GABAA receptors as apositive allosteric modulator.[13]
Other pregnane neurosteroids includealfadolone,alfaxolone,hydroxydione,minaxolone,pregnanolone (eltanolone), andrenanolone, among others.[14]
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.[4] 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.[4] Forty-four (40.7%) of the participants were from US sites.[4] Safety was assessed from a pool of two clinical studies.[4] 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.[4]
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