Ganaxolone

DEA Schedule V Controlled Substance -> Depressants

Pharmaceuticals -> Listed in ZINC15

Breast Feeding; Lactation; Milk, Human; Anticonvulsants; GABA Agents

FDA approved drugs -> Active ingredient

EMA approved medicines: Human medicine (Orphan designations)

FDA approved drugs -> Active ingredient

Warning

H302+H312+H332 (94.4%): Harmful if swallowed, in contact with skin or if inhaled [Warning Acute toxicity, oral; acute toxicity, dermal; acute toxicity, inhalation]

P261, P264, P270, P271, P280, P301+P317, P302+P352, P304+P340, P317, P321, P330, P362+P364, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 18 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

N - Nervous system

QN - Nervous system

Ganaxolone - like other neurosteroids - lacks classical hormonal activity, and instead appears to exert its effects directly via modulation of GABA_A receptors. Similar to other antiepileptic drugs, ganaxolone has been associated with significant somnolence and sedation - patients should be instructed to use caution when operating heavy machinery (e.g. driving). In addition, antiepileptic drugs may increase the risk of suicidal behaviour and ideation, although this risk has not been documented directly in patients taking ganaxolone. When considering ganaxolone therapy, clinicians should balance the risk of suicidal thoughts or behaviours with the risk of untreated illness. Ganaxolone drug scheduling is currently under review by the US Drug Enforcement Administration (DEA), but it appears to carry some potential for abuse. Clinicians should consider assessing for a history of drug abuse when deciding to initiate therapy with ganaxolone.

Ganaxolone belongs to a novel class of neuroactive steroids sometimes referred to as "epalons", which are potent and specific positive allosteric modulators of γ-aminobutyric acid type A (GABA_A) receptors in the central nervous system (CNS). It binds GABA_A at one of several potential binding sites, all of which are distinct from the benzodiazepine binding site. By enhancing the inhibitory effects of GABA_A receptors, endogenous and exogenous neurosteroids have been associated with anxiolytic, sedative, and anticonvulsant effects, amongst others. While the precise mechanism of action of ganaxolone in the treatment of seizures associated with CDD is unknown, its anticonvulsant effects are likely due to positive allosteric GABA_A modulation

Ganaxolone is extensively metabolized, primarily by CYP3A4/5 and, to a lesser extent, CYP2B6, CYP2C19, and CYP2D6. While data regarding ganaxolone metabolism are lacking, a 16-OH metabolite generated via CYP3A4 metabolism has been identified as one of its major metabolites.

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GANAXOLONE

Established Pharmacologic Class [EPC] - Neuroactive Steroid Gamma-Aminobutyric Acid A Receptor Positive Modulator

Mechanisms of Action [MoA] - GABA A Receptor Positive Modulators

Ganaxolone is a Neuroactive Steroid Gamma-Aminobutyric Acid A Receptor Positive Modulator. The mechanism of action of ganaxolone is as a GABA A Receptor Positive Modulator.

GANAXOLONE

Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.

Endogenous compounds or drugs that affect neuronal excitability through modulation of specific ionotropic receptors (e.g., GABA-A RECEPTORS). Endogenous neurosteroids are steroid hormones de novo synthesized by neurons and glial cells from steroid metabolite precursors (e.g., PREGNENOLONE).

Following oral administration, maximum plasma concentrations are reached within 2 to 3 hours.

Following a single oral dose of radiolabeled ganaxolone in healthy male subjects, 55% of the administered radioactivity was recovered in the feces (2% as unchanged parent drug) and 18% was recovered in the urine (none of which comprised unchanged parent drug).

Both ganaxolone and its metabolites are widely distributed into tissues following oral administration, with a typical tissue-to-plasma ratio >5:1.