List of neurosteroids

Neurosteroids are 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

• 25-Hydroxycholesterol: cholest-5-en-3β,25-diol – NMDA receptor negative allosteric modulator

Androstanes

• 3α,5α-Androstanediol (3α-androstanediol): 5α-androstane-3α,17β-diol – GABA_A receptor positive allosteric modulator
• 3α,5β-Androstanediol (etiocholanediol): 5β-androstane-3α,17β-diol – GABA_A receptor positive allosteric modulator
• 3α-Androstenol: 5α-androst-16-en-3α-ol – GABA_A receptor positive allosteric modulator
• Androsterone: 5α-androstan-3α-ol-17-one – GABA_A receptor positive allosteric modulator
• Etiocholanolone: 5β-androstan-3α-ol-17-one – GABA_A receptor positive allosteric modulator

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

The following are proneurosteroids:

• Deoxycorticosterone (desoxycortone): 21-hydroxypregn-4-ene-3,20-dione – of DHDOC and THDOC
• Pregnenolone (P5): pregn-5-en-3β-ol-20-one – of pregnanolones and pregnanediols (see above)
• Progesterone (P4): pregn-4-ene-3,20-dione – of pregnanediones, pregnanolones, and pregnanediols (see above)

Synthetic

Cholestanes

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

Pregnanes

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

The following are proneurosteroids:

• EIDD-1723 – of EIDD-036 (see above)
• P1-185 – of progesterone and by extension pregnanediones, pregnanolones, and pregnanediols (see above)
• Progesterone carboxymethyloxime (P4-3-CMO) – of progesterone and by extension pregnanediones, pregnanolones, and pregnanediols (see above)

Excitatory

Natural

Cholestanes

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

Pregnanes

• 3β-Dihydroprogesterone (3β-DHP): pregn-4-en-3β-ol-20-one – GABA_A receptor negative allosteric modulator
• Epipregnanolone: 5β-pregnan-3β-ol-20-one – GABA_A receptor negative allosteric modulator
• Isopregnanolone (sepranolone): 5α-pregnan-3β-ol-20-one – GABA_A receptor negative allosteric modulator
• Pregnenolone sulfate (PS): pregn-5-en-3β-ol-20-one 3β-sulfate – GABA_A 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 – GABA_A 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 – GABA_A 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 – GABA_A receptor negative allosteric modulator
• Golexanolone (GR-3027): 3α-ethynyl-3β-hydroxyandrostan-17E-one oxime – GABA_A receptor negative allosteric modulator

Others

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

Mixed

Natural

Cholestanes

• Cholesterol: cholest-5-en-3β-ol – NMDA receptor positive allosteric modulator, possible GABA_A receptor positive allosteric modulator, many other actions

Pregnanes

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

Neurotrophic

Natural

Androstanes

• Dehydroepiandrosterone (DHEA; prasterone): androst-5-en-3β-ol-17-one – TrkA, TrkC, and p75^NTR agonist, TrkB ligand
• Dehydroepiandrosterone sulfate (DHEA-S; prasterone sulfate): androst-5-en-3β-ol-17-one 3β-sulfate – TrkA and p75^NTR agonist

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

Synthetic

Androstanes

• BNN-20: 17β-spiro-(androst-5-en-17,2'-oxiran)-3β-ol – TrkA, TrkB, and p75^NTR agonist

Pregnanes

• BNN-27: 17α,20R-epoxypregn-5-ene-3β,21-diol – TrkA and p75^NTR agonist

Antineurotrophic

Natural

Androstanes

• Testosterone: androst-4-en-17β-ol-3-one – TrkA and p75^NTR antagonist

Synthetic

Pregnanes

• Dexamethasone: 9α-fluoro-11β,17α,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione – TrkA and p75^NTR antagonist

Pheromones and pherines

Natural

Androstanes

• 3α-Androstenol: 5α-androst-16-en-3α-ol
• 3β-Androstenol: 5α-androst-16-en-3β-ol
• Androstadienol: androsta-5,16-dien-3β-ol
• Androstadienone: androsta-4,16-dien-3-one
• Androstenone: 5α-androst-16-en-3-one
• Androsterone: 5α-androstan-3α-ol-17-one

Estranes

• Estratetraenol: estra-1,3,5(10),16-tetraen-3-ol

Synthetic

Androstanes

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

Estranes

• Estratetraenyl acetate (ETA): estra-1,3,5(10),16-tetraen-3-yl acetate

Pregnanes

• Pregnadienedione (PDD): pregna-4,20-dien-3,6-dione

Others

• PH10, PH15, PH30, PH56, PH78, PH84, Salubrin (PH80) – pherines with undefined structures developed by a company called Pherin Pharmaceuticals

Others

Natural

Pregnanes

• Pregnenolone (P5): pregn-5-en-3β-ol-20-one – MAP2 ligand
• Progesterone (P4): pregn-4-ene-3,20-dione – sigma-1 receptor antagonist, nicotinic acetylcholine receptor negative allosteric modulator, MAP2 ligand, other actions

Spirostanes

• Caprospinol (SP-233; diosgenin 3-caproate): (22R,25R)-20α-spirost-5-en-3β-yl hexanoate – β-amyloid ligand, sigma-1 receptor ligand, other actions; found naturally in Gynura japonica; under development as a neuroprotective against Alzheimer's disease

Estranes

• Estradiol (E2): Estra-1,3,5(10)-triene-3,17β-diol; found to increase the expression of the oxytocin receptor.

Synthetic

Pregnanes

• 3β-Methoxypregnenolone (MAP-4343): 3β-methoxypregn-5-en-20-one – MAP2 ligand
• Cyclopregnol (neurosterone): 6β-hydroxy-3:5-cyclopregnan-20-one – undefined mechanism of action; developed as a "psychotropic agent" for the treatment of "mental disorders" such as schizophrenia in the 1950s

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

• List of steroids
• Neurosteroidogenesis inhibitor

References