List of neurosteroids

From Wikipedia, the free encyclopedia
Jump to: navigation, search
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 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): 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
  • 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

The following are proneurosteroids:

  • P1-185 – of progesterone and by extension pregnanediones, pregnanolones, and pregnanediols (see above)

Excitatory[edit]

Natural[edit]

Cholestanes[edit]

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

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

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[6][7][8]

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[9]

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. PMC 4107067Freely accessible. PMID 24878244. doi:10.1016/j.neuropharm.2014.05.027. 
  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. PMID 16415088. doi:10.1124/jpet.105.098319. 
  3. ^ a b Kaminski RM, Marini H, Kim WJ, Rogawski MA (2005). "Anticonvulsant activity of androsterone and etiocholanolone". Epilepsia. 46 (6): 819–27. PMC 1181535Freely accessible. PMID 15946323. doi:10.1111/j.1528-1167.2005.00705.x. 
  4. ^ a b Belelli D, Lambert JJ, Peters JA, Gee KW, Lan NC (1996). "Modulation of human recombinant GABAA receptors by pregnanediols". Neuropharmacology. 35 (9-10): 1223–31. PMID 9014137. 
  5. ^ 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. PMC 3812502Freely accessible. PMID 24174662. doi:10.1523/JNEUROSCI.2619-13.2013. 
  6. ^ 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. PMC 4017285Freely accessible. PMID 24806926. doi:10.1016/j.bpj.2014.03.024. 
  7. ^ Levitan I, Singh DK, Rosenhouse-Dantsker A (2014). "Cholesterol binding to ion channels". Front Physiol. 5: 65. PMC 3935357Freely accessible. PMID 24616704. doi:10.3389/fphys.2014.00065. 
  8. ^ Lange Y, Steck TL (2016). "Active membrane cholesterol as a physiological effector". Chem. Phys. Lipids. 199: 74–93. PMID 26874289. doi:10.1016/j.chemphyslip.2016.02.003. 
  9. ^ Nozawa Y, Sakai N, Matsumoto K, Mizoue K (2002). "A novel neuritogenic compound, NGA0187". J. Antibiot. 55 (7): 629–34. PMID 12243452. 
  10. ^ Papadopoulos V, Lecanu L (2012). "Caprospinol: discovery of a steroid drug candidate to treat Alzheimer's disease based on 22R-hydroxycholesterol structure and properties". J. Neuroendocrinol. 24 (1): 93–101. PMID 21623958. doi:10.1111/j.1365-2826.2011.02167.x. 
  11. ^ http://adisinsight.springer.com/drugs/800017449