Ganaxolone
Chemical compound
From Wikipedia, the free encyclopedia
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][3] Ganaxolone is a neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator.[1]
 | |
| Clinical data | |
|---|---|
| Trade names | Ztalmy |
| Other names | GNX; CCD-1042; 3β-Methyl-5α-pregnan-3α-ol-20-one; 3α-Hydroxy-3β-methyl-5α-pregnan-20-one |
| License data |
|
| Routes of administration | By mouth |
| Drug class | Neurosteroid |
| ATC code | |
| Legal status | |
| Legal status |
|
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.210.937 |
| Chemical and physical data | |
| Formula | C22H36O2 |
| Molar mass | 332.528 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
  (what is this?) (verify) | |
The most common side effects of treatment with ganaxolone include somnolence (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 US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[6][7]
Medical uses
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.[10][11]
Ganaxolone is thought to modulate both synaptic and extrasynaptic GABAA receptors to normalize over-excited neurons.[3] 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.[3]
Ganaxolone binds to allosteric sites of the GABAA receptor to modulate and open the chloride ion channel, resulting in a hyperpolarization of the neuron.[3] This causes an inhibitory effect on neurotransmission, reducing the chance of a successful action potential (depolarization) from occurring.[3][10][11]
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.[12]
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.[13]
Other pregnane neurosteroids include alfadolone, alfaxolone, hydroxydione, minaxolone, pregnanolone (eltanolone), and renanolone, among others.[14]
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.[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]
