List of neurosteroids
This is a list of neurosteroids, or
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
- negative allosteric modulator[1]
Androstanes
- positive allosteric modulator
- 3α,5β-Androstanediol(etiocholanediol): 5β-androstane-3α,17β-diol – GABAA receptor positive allosteric modulator
- 3α-Androstenol: 5α-androst-16-en-3α-ol – GABAA receptor positive allosteric modulator[2]
- Androsterone: 5α-androstan-3α-ol-17-one – GABAA receptor positive allosteric modulator[3]
- Etiocholanolone: 5β-androstan-3α-ol-17-one – GABAA receptor positive allosteric modulator[3]
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]
- 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:
- 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 – 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:
- EIDD-1723 – of EIDD-036 (see above)[5]
- P1-185 – of progesterone and by extension pregnanediones, pregnanolones, and pregnanediols (see above)[8][9]
- Progesterone carboxymethyloxime (P4-3-CMO) – of progesterone and by extension pregnanediones, pregnanolones, and pregnanediols (see above)[10][11]
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
- TrkB ligand
- Dehydroepiandrosterone sulfate (DHEA-S; prasterone sulfate): androst-5-en-3β-ol-17-one 3β-sulfate – TrkA and p75NTR agonist
Ergostanes
- 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
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
- (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
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
- psychotropic agent" for the treatment of "mental disorders" such as schizophreniain the 1950s
Androstanes
- tranquilizer" and for the treatment of alcoholismin the 1950s
See also
References
- PMID 24878244.
- S2CID 95393004.
- ^ PMID 15946323.
- ^ S2CID 10437944.
- ^ S2CID 19906601.
- ^ PMID 29223589.
- PMID 28753313.
- PMID 19791804.
- PMID 24900479.
- ISSN 0378-5173.
- ISSN 0378-5173.
- PMID 24174662.
- PMID 24806926.
- PMID 24616704.
- PMID 26874289.
- PMID 12243452.
- S2CID 24032303.
- ^ "Research programme: Neurodegenerative disorders therapeutics - Samaritan/McGill University - AdisInsight".