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 (CDD).Ganaxolone was approved for medical use in the United States in March 2022. 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.Ganaxolone is thought to modulate both synaptic and extrasynaptic GABAA receptors to normalize over-excited neurons. Ganaxolones activation of the extrasynaptic receptor is an additional mechanism that provides stabilizing effects that potentially differentiates it from other drugs that increase GABA signaling.Ganaxolone binds to allosteric sites of the GABAA receptor to modulate and open the chloride ion channel, resulting in a hyperpolarization of the neuron. This causes an inhibitory effect on neurotransmission, reducing the chance of a successful action potential (depolarization) from occurring.It is unknown if ganaxolone possesses significant hormonal activity in vivo, with a 2020 study finding evidence of in vitro binding to the membrane progesterone receptor. Chemistry
Ganaxolone is a analog of the neuroactive steroid allopregnanolone which possesses no known hormonal activity and, instead, is thought to primarily function by binding to GABAa receptors as a positive allosteric modulator.Other pregnane neurosteroids include alfadolone, alfaxolone, allopregnanolone (brexanolone), hydroxydione, minaxolone, pregnanolone (eltanolone), and renanolone, among others. Research
Ganaxolone is being investigated for potential medical use in the treatment of epilepsy. It is well tolerated in human trials, with the most commonly reported side effects being somnolence (sleepiness), dizziness, and fatigue.
Opioids, in overdose or combined with other depressants, are notorious for such fatalities. Treatment
Respiratory stimulants such as nikethamide were traditionally used to counteract respiratory depression from CNS depressant overdose, but offered limited effectiveness. A new respiratory stimulant drug called BIMU8 is being investigated which seems to be significantly more effective and may be useful for counteracting the respiratory depression produced by opiates and similar drugs without offsetting their therapeutic effects. If the respiratory depression occurs from opioid overdose, usually an opioid antagonist, most likely naloxone, will be administered. This will rapidly reverse the respiratory depression unless complicated by other depressants. However an opioid antagonist may also precipitate an opioid withdrawal syndrome in chronic users. Mechanical ventilation may still be necessary during initial resuscitation. Associated conditions
Disorders like congenital central hypoventilation syndrome (CCHS) and ROHHAD (rapid-onset obesity, hypothalamic dysfunction, hypoventilation, with autonomic dysregulation) are recognized as conditions that are associated with hypoventilation. CCHS may be a significant factor in some cases of sudden infant death syndrome (SIDS), often termed "cot death" or "crib death". The opposite condition is hyperventilation (too much ventilation), resulting in low carbon dioxide levels (hypocapnia), rather than hypercapnia. See also
Dyspnea
Hyperventilation
List of terms of lung size and activity


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