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Chemical Compound Review

SureCN678181     1-[(3R,5S,10S,13S,17S)-3- hydroxy-3,10,13...

Synonyms: CHEBI:370090, AC1L1YWW, LS-118581, FT-0630602, C22H36O2, ...
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Disease relevance of GANAXOLONE


Psychiatry related information on GANAXOLONE

  • The ED50 and lower doses of ganaxolone prevented the observed behavioral effects of PTZ as well as its depressant effects on locomotor activity and rearing of mice [5].

High impact information on GANAXOLONE

  • Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) is a novel neurosteroid which has anticonvulsant properties in a number of seizure models as well as the ability to enhance function of the gamma-aminobutyric acid-A (GABA(A)) receptor complex via a neurosteroid binding site [1].
  • Their structural specificity in both models corresponds with their activities as positive allosteric modulators of GABAA receptors, although ganaxolone is more potent than expected, probably because it has greater bioavailability [6].
  • RESULTS: The neuroactive steroids prevented 6-Hz seizures with rank order of potencies (ED50 values): ganaxolone (6.3 mg/kg) > 5alpha,3alpha-P (14.2 mg/kg) > or = 5beta,3alpha-P (14.4 mg/kg) > 5alpha,3beta-P (>100 mg/kg) [6].
  • Exposure of cultured rat cerebellar granule cells to 1 microM ganaxolone for 5 days had no effect on the abundance of mRNAs encoding the alpha1, alpha2, alpha3, alpha4, alpha5, gamma2L, or gamma2S subunits of the GABA(A) receptor [7].
  • Changes in GABA(A) receptor gene expression induced by withdrawal of, but not by long-term exposure to, ganaxolone in cultured rat cerebellar granule cells [7].

Biological context of GANAXOLONE


Anatomical context of GANAXOLONE


Associations of GANAXOLONE with other chemical compounds


Gene context of GANAXOLONE

  • Ganaxolone is an efficacious anticonvulsant agent in a variety of acute seizure models, as well as in electrical and chemical kindling models, and is currently under Phase II clinical investigation for epilepsy [5].
  • Thus, synthetic neuroactive steroids, such as ganaxolone, which are orally active and devoid of hormonal side effects, represent a novel treatment strategy for catamenial epilepsy [12].

Analytical, diagnostic and therapeutic context of GANAXOLONE

  • RESULTS: We found that ganaxolone 30 mg/kg significantly increased the ED(50) in the bioassay, for a potency ratio of 1.8+/-0.41 compared with vehicle (P<0.05) [2].
  • During this state of enhanced seizure susceptibility, there was a 3-fold increase in the anticonvulsant potency of ganaxolone (control ED(50) = 3.5 mg/kg; withdrawn = 1.2 mg/kg) without a change in the potency for induction of motor toxicity in the rotarod test [4].


  1. Ganaxolone, a selective, high-affinity steroid modulator of the gamma-aminobutyric acid-A receptor, exacerbates seizures in animal models of absence. Snead, O.C. Ann. Neurol. (1998) [Pubmed]
  2. Effect of ganaxolone in a rodent model of cerebral hematoma. Lyden, P., Shin, C., Jackson-Friedman, C., Hassid, S., Chong, A., Macdonald, R.L. Stroke (2000) [Pubmed]
  3. Effect of ganaxolone on flurothyl seizures in developing rats. Liptáková, S., Velísek, L., Velísková, J., Moshé, S.L. Epilepsia (2000) [Pubmed]
  4. Enhanced anticonvulsant activity of ganaxolone after neurosteroid withdrawal in a rat model of catamenial epilepsy. Reddy, D.S., Rogawski, M.A. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  5. Reversal of behavioral effects of pentylenetetrazol by the neuroactive steroid ganaxolone. Beekman, M., Ungard, J.T., Gasior, M., Carter, R.B., Dijkstra, D., Goldberg, S.R., Witkin, J.M. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
  6. Allopregnanolone analogs that positively modulate GABA receptors protect against partial seizures induced by 6-Hz electrical stimulation in mice. Kaminski, R.M., Livingood, M.R., Rogawski, M.A. Epilepsia (2004) [Pubmed]
  7. Changes in GABA(A) receptor gene expression induced by withdrawal of, but not by long-term exposure to, ganaxolone in cultured rat cerebellar granule cells. Mascia, M.P., Biggio, F., Mancuso, L., Cabras, S., Cocco, P.L., Gorini, G., Manca, A., Marra, C., Purdy, R.H., Follesa, P., Biggio, G. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  8. Initial human experience with ganaxolone, a neuroactive steroid with antiepileptic activity. Monaghan, E.P., Navalta, L.A., Shum, L., Ashbrook, D.W., Lee, D.A. Epilepsia (1997) [Pubmed]
  9. Allopregnanolone and ganaxolone increase the firing activity of dorsal raphe nucleus serotonergic neurons in female rats. Robichaud, M., Debonnel, G. Int. J. Neuropsychopharmacol. (2006) [Pubmed]
  10. The contraceptive agent Provera enhances GABA(A) receptor-mediated inhibitory neurotransmission in the rat hippocampus: evidence for endogenous neurosteroids? Belelli, D., Herd, M.B. J. Neurosci. (2003) [Pubmed]
  11. Modification of behavioral effects of drugs in mice by neuroactive steroids. Ungard, J.T., Beekman, M., Gasior, M., Carter, R.B., Dijkstra, D., Witkin, J.M. Psychopharmacology (Berl.) (2000) [Pubmed]
  12. Role of neurosteroids in catamenial epilepsy. Reddy, D.S. Epilepsy Res. (2004) [Pubmed]
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