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List of neurosteroids

Allopregnanolone, a major endogenous inhibitory neurosteroid.
Steroid ring system.

This is a list of neurosteroids, or natural and synthetic steroids that are active on the mammalian nervous system through receptors other than steroid hormone receptors. It includes inhibitory, excitatory, and neurotrophic neurosteroids as well as pheromones and vomeropherines. In contrast to steroid hormones, neurosteroids have rapid, non-genomic effects through interactions with membrane steroid receptors and can quickly influence central nervous system function.

Inhibitory

Natural

Cholestanes

Androstanes

The following are proneurosteroids:

  • Dihydrotestosterone (DHT; androstanolone, stanolone): 5α-androst-17β-ol-3-one – of the above-listed inhibitory androstane neurosteroids
  • Testosterone: androst-4-en-17β-ol-3-one – of the above-listed inhibitory androstane neurosteroids

Pregnanes

  • 3α-Dihydroprogesterone (3α-DHP): pregn-4-en-3α-ol-20-one – GABAA receptor positive allosteric modulator
  • 5α-Dihydroprogesterone (5α-DHP; allopregnanedione): 5α-pregnane-3,20-dione – GABAA receptor positive allosteric modulator
  • 5β-Dihydroprogesterone (5β-DHP; pregnanedione): 5β-pregnane-3,20-dione – GABAA receptor positive allosteric modulator
  • Allopregnanediol: 5α-pregnane-3α,20α-diol – GABAA receptor positive allosteric modulator[4]
  • Allopregnanolone (brexanolone; SAGE-547): 5α-pregnan-3α-ol-20-one – GABAA receptor positive allosteric modulator
  • Dihydrodeoxycorticosterone (DHDOC): 21-hydroxy-5α-pregnan-20-one – GABAA receptor positive allosteric modulator
  • Pregnanediol: 5β-pregnan-3α,20α-diol – GABAA receptor positive allosteric modulator[4]
  • Pregnanolone (eltanolone): 5β-pregnan-3α-ol-20-one – GABAA receptor positive allosteric modulator
  • Tetrahydrodeoxycorticosterone (THDOC): 3α,21-dihydroxy-5α-pregnan-20-one – GABAA receptor positive allosteric modulator

The following are proneurosteroids:

Synthetic

Cholestanes

  • Acebrochol (cholesteryl acetate dibromide): 5α,6β-dibromocholestan-3β-ol 3β-acetate – GABAA receptor positive allosteric modulator

Pregnanes

  • Alfadolone: 3α,21-dihydroxy-5α-pregnane-11,20-dione – GABAA receptor positive allosteric modulator
  • Alfadolone acetate: 3α,21-dihydroxy-5α-pregnane-11,20-dione 21-acetate – GABAA receptor positive allosteric modulator
  • Alfaxalone: 3α-hydroxy-5α-pregnane-11,20-dione – GABAA receptor positive allosteric modulator
  • EIDD-036 (P4-20-O): 20-(hydroxyimino)pregn-4-en-3-one – progesterone-like inhibitory neurosteroid[5]
  • Ganaxolone: 3β-methyl-5α-pregnan-3α-ol-20-one – GABAA receptor positive allosteric modulator
  • Hydroxydione: 21-hydroxy-5β-pregnane-3,20-dione – GABAA receptor positive allosteric modulator
  • Minaxolone: 11α-(dimethylamino)-2β-ethoxy-5α-pregnan-3α-ol-20-one – GABAA receptor positive allosteric modulator
  • ORG-20599: 21-chloro-2β-morpholin-4-yl-5β-pregnan-3α-ol-20-one – GABAA receptor positive allosteric modulator
  • ORG-21465: 2β-(2,2-dimethyl-4-morpholinyl)-3α-hydroxy-11,20-dioxo-5α-pregnan-21-yl methanesulfonate – GABAA receptor positive allosteric modulator
  • Posovolone (Co 134444): 3β-Hydroxy-21-(1H-imidazol-1-yl)-3α-(methoxymethyl)-5α-pregnan-20-one – GABAA receptor positive allosteric modulator
  • Renanolone: 5β-pregnan-3α-ol-11,20-dione – GABAA receptor positive allosteric modulator
  • SGE-516 – GABAA receptor positive allosteric modulator[6]
  • SGE-872 – GABAA receptor positive allosteric modulator[6]
  • Zuranolone (SAGE-217): 3α-hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one – GABAA receptor positive allosteric modulator[7][6]

The following are proneurosteroids:

Excitatory

Natural

Cholestanes

  • Cerebrosterol (24(S)-Hydroxycholesterol): cholest-5-en-3β,24S-diol – NMDA receptor positive allosteric modulator[12]

Pregnanes

  • 3β-Dihydroprogesterone (3β-DHP): pregn-4-en-3β-ol-20-one – GABAA receptor negative allosteric modulator
  • Epipregnanolone: 5β-pregnan-3β-ol-20-one – GABAA receptor negative allosteric modulator
  • Isopregnanolone (sepranolone): 5α-pregnan-3β-ol-20-one – GABAA receptor negative allosteric modulator
  • Pregnenolone sulfate (PS): pregn-5-en-3β-ol-20-one 3β-sulfate – GABAA receptor negative allosteric modulator, NMDA receptor positive allosteric modulator, sigma-1 receptor agonist, TRPM3 agonist, other actions

The following are proneurosteroids:

  • Pregnenolone (P5): pregn-5-en-3β-ol-20-one – of pregnenolone sulfate

Androstanes

  • Dehydroepiandrosterone (DHEA; prasterone): androst-5-en-3β-ol-17-one – GABAA receptor positive allosteric modulator, NMDA receptor positive allosteric modulator, sigma-1 receptor agonist, other actions
  • Dehydroepiandrosterone sulfate (DHEA-S; prasterone sulfate): androst-5-en-3β-ol-17-one 3β-sulfate – GABAA receptor negative allosteric modulator, NMDA receptor positive allosteric modulator, other actions

Synthetic

Androstanes

  • 17-Phenylandrostenol (17-PA): 17-phenyl-5α-androst-16-en-3α-ol – GABAA receptor negative allosteric modulator
  • Golexanolone (GR-3027): 3α-ethynyl-3β-hydroxyandrostan-17E-one oxime – GABAA receptor negative allosteric modulator

Others

  • SAGE-201 - oxysterol/cholesterol analogue – NMDA receptor positive allosteric modulator[6]
  • SAGE-301 - oxysterol/cholesterol analogue – NMDA receptor positive allosteric modulator[6]
  • SAGE-718: oxysterol/cholesterol analogue; exact chemical structure undisclosed – NMDA receptor positive allosteric modulator[6]

Mixed

Natural

Cholestanes

  • Cholesterol: cholest-5-en-3β-ol – NMDA receptor positive allosteric modulator, possible GABAA receptor positive allosteric modulator, many other actions[13][14][15]

Pregnanes

  • Epipregnanolone sulfate: 5β-pregnan-3β-ol-20-one 3β-sulfate – GABAA and NMDA receptor negative allosteric modulator, TRPM3 agonist

Neurotrophic

Natural

Androstanes

Ergostanes

  • Anicequol (NGA0187, NGD-187): 16β-acetoxy-3β,7β,11β-trihydroxy-5α-ergost-22(E)-en-6-one – non-endogenous; fungi-derived; undefined mechanism of action; shows neurotrophic activity in vitro; was formerly under development for the treatment of cognitive disorders[16]

Synthetic

Androstanes

  • BNN-20: 17β-spiro-(androst-5-en-17,2'-oxiran)-3β-ol – TrkA, TrkB, and p75NTR agonist

Pregnanes

  • BNN-27: 17α,20R-epoxypregn-5-ene-3β,21-diol – TrkA and p75NTR agonist

Antineurotrophic

Natural

Androstanes

  • Testosterone: androst-4-en-17β-ol-3-one – TrkA and p75NTR antagonist

Synthetic

Pregnanes

  • Dexamethasone: 9α-fluoro-11β,17α,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione – TrkA and p75NTR antagonist

Pheromones and pherines

See also: Pheromone § Humans, Sex pheromone § In_humans, and Pherine

Natural

Androstanes

Estranes

Synthetic

Androstanes

  • Fasedienol (Aloradine; PH94B; 4-androstadienol): androsta-4,16-dien-3β-ol

Estranes

Pregnanes

Others

Others

Natural

Pregnanes

Spirostanes

See also: spiro compound, diosgenin, and caproate

Estranes

Synthetic

Pregnanes

Androstanes

  • Cetadiol: androst-5-ene-3β,16α-diol – undefined mechanism of action; developed as a "tranquilizer" and for the treatment of alcoholism in the 1950s

See also

References

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