List of neurosteroids

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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[edit]

Natural[edit]

Cholestanes[edit]

Androstanes[edit]

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[edit]

  • 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[edit]

Cholestanes[edit]

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

Pregnanes[edit]

  • 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
  • Renanolone: 5β-pregnan-3α-ol-11,20-dione – GABAA receptor positive allosteric modulator
  • SAGE-217: 3α-hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one – GABAA receptor positive allosteric modulator[6][7]
  • SGE-516 (SAGE-516) – GABAA receptor positive allosteric modulator[7]
  • SGE-872 (SAGE-872) – GABAA receptor positive allosteric modulator[7]

The following are proneurosteroids:

Excitatory[edit]

Natural[edit]

Cholestanes[edit]

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

Pregnanes[edit]

  • 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[edit]

  • 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 positive allosteric modulator, NMDA receptor positive allosteric modulator, other actions

Synthetic[edit]

Androstanes[edit]

  • 17-Phenylandrostenol (17-PA): 17-phenyl-5α-androst-16-en-3α-ol – GABAA receptor negative allosteric modulator

Others[edit]

  • SAGE-201 (SGE-201): oxysterol/cholesterol analogue – NMDA receptor positive allosteric modulator[7]
  • SAGE-301 (SGE-301): oxysterol/cholesterol analogue – NMDA receptor positive allosteric modulator[7]
  • SAGE-718: oxysterol/cholesterol analogue; exact chemical structure undisclosed – NMDA receptor positive allosteric modulator[7]

Mixed[edit]

Natural[edit]

Cholestanes[edit]

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

Pregnanes[edit]

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

Neurotrophic[edit]

Natural[edit]

Androstanes[edit]

Ergostanes[edit]

  • 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[edit]

Androstanes[edit]

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

Pregnanes[edit]

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

Antineurotrophic[edit]

Natural[edit]

Androstanes[edit]

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

Synthetic[edit]

Pregnanes[edit]

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

Pheromones and pherines[edit]

Natural[edit]

Androstanes[edit]

Estranes[edit]

Synthetic[edit]

Androstanes[edit]

Estranes[edit]

Pregnanes[edit]

Others[edit]

Others[edit]

Natural[edit]

Pregnanes[edit]

Spirostanes[edit]

Synthetic[edit]

Pregnanes[edit]

Androstanes[edit]

  • 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[edit]

References[edit]

  1. ^ Linsenbardt AJ, Taylor A, Emnett CM, Doherty JJ, Krishnan K, Covey DF, Paul SM, Zorumski CF, Mennerick S (2014). "Different oxysterols have opposing actions at N-methyl-D-aspartate receptors". Neuropharmacology. 85: 232–42. doi:10.1016/j.neuropharm.2014.05.027. PMC 4107067Freely accessible. PMID 24878244. 
  2. ^ Kaminski RM, Marini H, Ortinski PI, Vicini S, Rogawski MA (2006). "The pheromone androstenol (5 alpha-androst-16-en-3 alpha-ol) is a neurosteroid positive modulator of GABAA receptors". J. Pharmacol. Exp. Ther. 317 (2): 694–703. doi:10.1124/jpet.105.098319. PMID 16415088. 
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  6. ^ Martinez Botella G, Salituro FG, Harrison BL, Beresis RT, Bai Z, Blanco MJ, Belfort GM, Dai J, Loya CM, Ackley MA, Althaus AL, Grossman SJ, Hoffmann E, Doherty JJ, Robichaud AJ (2017). "Neuroactive Steroids. 2. 3α-Hydroxy-3β-methyl-21-(4-cyano-1H-pyrazol-1'-yl)-19-nor-5β-pregnan-20-one (SAGE-217): A Clinical Next Generation Neuroactive Steroid Positive Allosteric Modulator of the (γ-Aminobutyric Acid)A Receptor". J. Med. Chem. 60 (18): 7810–7819. doi:10.1021/acs.jmedchem.7b00846. PMID 28753313. 
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  11. ^ Basu, Krishnakali; Kildsig, Dane O.; Mitra, Ashim K. (1988). "Synthesis and kinetic stability studies of progesterone derivatives". International Journal of Pharmaceutics. 47 (1-3): 195–203. doi:10.1016/0378-5173(88)90231-1. ISSN 0378-5173. 
  12. ^ Paul SM, Doherty JJ, Robichaud AJ, Belfort GM, Chow BY, Hammond RS, Crawford DC, Linsenbardt AJ, Shu HJ, Izumi Y, Mennerick SJ, Zorumski CF (2013). "The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors". J. Neurosci. 33 (44): 17290–300. doi:10.1523/JNEUROSCI.2619-13.2013. PMC 3812502Freely accessible. PMID 24174662. 
  13. ^ Hénin J, Salari R, Murlidaran S, Brannigan G (2014). "A predicted binding site for cholesterol on the GABAA receptor". Biophys. J. 106 (9): 1938–49. doi:10.1016/j.bpj.2014.03.024. PMC 4017285Freely accessible. PMID 24806926. 
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