Allopregnanolone

Allopregnanolone

IUPAC name 1-(3-hydroxy-10,13-dimethyl- 2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro- 1H-cyclopenta[a] phenanthren-17-yl)ethanone
Other names 3α,5α-Tetrahydroprogesterone
Identifiers
CAS number	516-54-1^Y
PubChem	262961
ChemSpider	17216124^Y
ChEMBL	CHEMBL38856^N
Jmol-3D images	Image 1
SMILES CC(=O)[C@H]2CC[C@H]1[C@@H]3CCC4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@@]12C
InChI InChI=1S/C21H34O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h14-19,23H,4-12H2,1-3H3/t14?,15-,16+,17-,18+,19+,20+,21-/m1/s1^Y Key: AURFZBICLPNKBZ-JMTGGFPBSA-N^Y InChI=1/C21H34O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h14-19,23H,4-12H2,1-3H3/t14?,15-,16+,17-,18+,19+,20+,21-/m1/s1 Key: AURFZBICLPNKBZ-JMTGGFPBBC
Properties
Molecular formula	C₂₁H₃₄O₂
Molar mass	318.49 g/mol
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Allopregnanolone (3α-hydroxy-5α-pregnan-20-one or 3α,5α-tetrahydroprogesterone) is a prototypic neurosteroid present in the blood and also the brain. It is a metabolite of progesterone and potent modulator of GABA_A receptors. While allopregnanolone, like other GABA_A receptor active neurosteroids such as allotetrahydrodeoxycorticosterone (3α,21-dihydroxy-5α-pregnan-20-one; THDOC), positively modulates all GABA_A receptor isoforms, those isoforms containing δ-subunits exhibit greater magnitude potentiation. Allopregnanolone has pharmacological properties similar to other positive modulators of GABA_A receptors, including anxiolytic and anticonvulsant activity.^[1]

The biosynthesis of allopregnanolone starts with the converting of progesterone into 5α-dihydroprogesterone by 5α-reductase type I. After that, 3α-hydroxysteroid oxidoreductase isoenzymes (also referred to as 3α-hydroxysteroid dehydrogenase) converts this intermediate into allopregnanolone. Anxiety and depression are common side effects of 5α-reductase inhibitors such as finasteride and dutasteride, and they are believed to be caused, in part, by the prevention of the endogenous production of allopregnanolone.

The 5β-epimer of this compound (pregnanolone; 3α-hydroxy-5β-pregnan-20-one) has similar properties to allopregnanolone, and the 3β-methyl analogue, ganaxolone, is under development to treat epilepsy and other conditions.

Allopregnanolone aids neurogenesis and has been found to reverse neuron creation and cognitive deficits in mouse model of Alzheimer’s disease.^[2]

References

^ Kokate TG, Svensson BE, Rogawski MA. Anticonvulsant activity of neurosteroids: correlation with gamma-aminobutyric acid-evoked chloride current potentiation. J Pharmacol Exp Ther. 1994 Sep;270(3):1223-9. PMID 7932175
^ Wang JM, Singh C, Liu L, Irwin RW, Chen S, Chung EJ, Thompson RF, Brinton RD. (2010). Allopregnanolone reverses neuron and cognitive deficits in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 107:6498–6503. doi:10.1073/pnas.1001422107 PMID 20231471

* Herd, MB,; Belelli D, Lambert JJ. (2007). Neurosteroid modulation of synaptic and extrasynaptic GABA(A) receptors. Pharmacol. Ther. 116(1):20-34. doi:10.1016/j.pharmthera.2007.03.007.

Kask K; Bäckström T; Nilsson LG; Sundström-Poromaa I (2008). "Allopregnanolone impairs episodic memory in healthy women". Psychopharmacology 199 (2): 161–8. doi:10.1007/s00213-008-1150-7. PMID 18551282.
Chen S; Wang JM; Irwin RW (2011). "Allopregnanolone Promotes Regeneration and Reduces β-Amyloid Burden in a Preclinical Model of Alzheimer's Disease". PLoS ONE 6 (8): e24293. doi:10.1371/journal.pone.0024293. PMC 3168882. PMID 21918687. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3168882.

Hypnotics/Sedatives (N05C)

GABA_A Agonists/PAMs	Barbiturates: Allobarbital • Amobarbital • Aprobarbital • Barbital • Butabarbital • Butobarbital • Cyclobarbital • Ethallobarbital • Heptabarb • Hexobarbital • Mephobarbital • Methohexital • Pentobarbital • Phenobarbital • Proxibarbal • Reposal • Secobarbital • Talbutal • Thiamylal • Thiopental • Vinbarbital • Vinylbital Benzodiazepines: Brotizolam • Clonazepam • Cinolazepam • Climazolam • Doxefazepam • Estazolam • Flunitrazepam • Flurazepam • Flutoprazepam • Haloxazolam • Loprazolam • Lorazepam •Lormetazepam • Midazolam • Nimetazepam • Nitrazepam • Quazepam • Temazepam • Triazolam Carbamates: Carisoprodol • Ethinamate • Hexapropymate • Meprobamate • Methocarbamol • Procymate • Tybamate Neuroactive Steroids: Acebrochol • Allopregnanolone • Alphadolone • Alphaxolone • Eltanolone • Ganaxolone • Hydroxydione • Minaxolone • Org 20599 • Org 21465 • Tetrahydrodeoxycorticosterone Nonbenzodiazepines: CL-218,872 • Eszopiclone • Indiplon • JM-1232 • Lirequinil • Necopidem • Pazinaclone • ROD-188 • Saripidem • Suproclone • Suriclone • SX-3228 • U-89843A • U-90042 • Zaleplon • Zolpidem • Zopiclone Phenols: Fospropofol • Propofol Piperidinediones: Glutethimide • Methyprylon • Pyrithyldione • Piperidione Quinazolinones: Afloqualone • Cloroqualone • Diproqualone • Etaqualone • Mebroqualone • Mecloqualone • Methaqualone • Methylmethaqualone • Nitromethaqualone Volatiles/gases: 2-Methyl-2-butanol • Acetophenone • Acetylglycinamide chloral hydrate • Centalun • Chloral hydrate • Ethanol (Alcohol) • Paraldehyde • Trichloroethanol Others: Bromide (Lithium bromide, Potassium bromide, Sodium bromide) • Chloralose • Chloralodol • Clomethiazole • Dichloralphenazone • Ethchlorvynol • Etomidate • Gaboxadol • Loreclezole • Methylpentynol • Metomidate • Org 25435 • Petrichloral • Sulfonmethane • Triclofos • Valerenic acid (Valerian)

GABA_B Agonists	1,4-Butanediol • Aceburic acid • GABOB • GHB (Sodium oxybate) • GBL • GVL

H₁ Inverse agonists	Antihistamines: Captodiame • Cyproheptadine • Diphenhydramine • Doxylamine • Hydroxyzine • Methapyrilene • Pheniramine • Promethazine • Propiomazine Antidepressants: Tricyclic antidepressants (Amitriptyline, Doxepin, Trimipramine, etc.) • Tetracyclic antidepressants (Mianserin, Mirtazapine, etc.) Antipsychotics: Typical antipsychotics (Chlorpromazine, Thioridazine, etc.) • Atypical antipsychotics (Olanzapine, Quetiapine, Risperidone, etc.)

α₁-Adrenergic Antagonists	Antidepressants: Serotonin antagonists and reuptake inhibitors (Trazodone) • Tricyclic antidepressants (Amitriptyline, Doxepin, Trimipramine, etc.) • Tetracyclic antidepressants (Mianserin) Antipsychotics: Typical antipsychotics (Chlorpromazine, Thioridazine, etc.) • Atypical antipsychotics (Olanzapine, Quetiapine, Risperidone, etc.) Others: Niaprazine

α₂-Adrenergic Agonists	4-NEMD • Clonidine • Detomidine • Dexmedetomidine • Lofexidine • Medetomidine • Romifidine • Tizanidine • Xylazine

5-HT_2A Antagonists	Antidepressants: Serotonin antagonists and reuptake inhibitors (Trazodone) • Tricyclic antidepressants (Amitriptyline, Doxepin, Trimipramine, etc.) • Tetracyclic antidepressants (Mianserin, Mirtazapine, etc.) Antipsychotics: Typical antipsychotics (Chlorpromazine, Thioridazine, etc.) • Atypical antipsychotics (Olanzapine, Quetiapine, Risperidone, etc.) Others: Eplivanserin • Niaprazine • Pruvanserin • Volinanserin

Melatonin Agonists	Agomelatine • LY-156,735 • Melatonin • Ramelteon • Tasimelteon

Orexin Antagonists	Almorexant • SB-334,867 • SB-408,124 • SB-649,868 • Suvorexant • TCS-OX2-29

Others	Acecarbromal • Apronal • Bromisoval • Cannabidiol (Cannabis) • Carbromal • Embutramide • Evoxine • Fenadiazole • Gabapentin • Kavalactones (Kava) • Mephenoxalone • Opioids (Oxycodone, Morphine (Opium), etc.) • Passion flower • Scopolamine (Mandrake) • Valnoctamide

Anxiolytics (N05B)

GABA_A PAMs

Benzodiazepine	Adinazolam • Alprazolam • Bretazenil • Bromazepam • Camazepam • Chlordiazepoxide • Clobazam • Clonazepam • Clorazepate • Clotiazepam • Cloxazolam • Diazepam • Ethyl Loflazepate • Etizolam • Fludiazepam • Halazepam • Imidazenil • Ketazolam • Lorazepam • Medazepam • Nordazepam • Oxazepam • Pinazepam • Prazepam

Carbamates	Emylcamate • Mebutamate • Meprobamate (Carisoprodol, Tybamate) • Phenprobamate • Procymate

Nonbenzodiazepines	Abecarnil • Adipiplon • Alpidem • CGS-8216 • CGS-9896 • CGS-13767 • CGS-20625 • Divaplon • ELB-139 • Fasiplon • GBLD-345 • Gedocarnil • L-838,417 • NS-2664 • NS-2710 • Ocinaplon • Pagoclone • Panadiplon • Pipequaline • RWJ-51204 • SB-205,384 • SL-651,498 • Taniplon • TP-003 • TP-13 • TPA-023 • Y-23684 • ZK-93423

Pyrazolopyridines	Cartazolate • Etazolate • ICI-190,622 • Tracazolate

Others	Chlormezanone • Ethanol (Alcohol) • Etifoxine • Kavalactones (Kava Kava) • Skullcap • Valerenic Acid (Valerian)

α₂δ VDCC Blockers

Gabapentin • Pregabalin

5-HT_1A Agonists

Azapirones: Buspirone • Gepirone • Tandospirone; Others: Flesinoxan • Oxaflozane

H₁ Antagonists

Diphenylmethanes: Captodiame • Hydroxyzine; Others: Brompheniramine • Chlorpheniramine • Pheniramine

CRH₁ Antagonists

Antalarmin • CP-154,526 • Pexacerfont • Pivagabine

NK₂ Antagonists

GR-159,897 • Saredutant

MCH₁ antagonists

ATC-0175 • SNAP-94847

mGluR₂_/₃ Agonists

DAA-1097 • DAA-1106 • Emapunil • FGIN-127 • FGIN-143

σ₁ agonists

Afobazole • Opipramol

Others

Benzoctamine • Carbetocin • Demoxytocin • Mephenoxalone • Mepiprazole • Oxanamide • Oxytocin • Promoxolane • Tofisopam • Trimetozine • WAY-267,464

^#WHO-EM. ^‡Withdrawn from market. Clinical trials: ^†Phase III. ^§Never to phase III

M: PSO/PSI

mepr

dsrd (o, p, m, p, a, d, s), sysi/epon, spvo

proc(eval/thrp), drug(N5A/5B/5C/6A/6B/6D)

Anticonvulsants (N03)

GABA_A receptor agonist

Barbiturates	Barbexaclone • Metharbital • Methylphenobarbital • Pentobarbital • Phenobarbital^# • Primidone

Benzodiazepines	Clobazam • Clonazepam • Clorazepate • Diazepam^# • Flutoprazepam • Lorazepam • Midazolam • Nimetazepam • Nitrazepam • Temazepam

Other GABA agents

Aromatic allylic alcohols	Stiripentol

Carbonic anhydrase inhibitor

Sulfa drugs	Acetazolamide • Ethoxzolamide • Sultiame • Zonisamide

Channel blockers

Primarily sodium

Hydantoins	Ethotoin • Fosphenytoin • Mephenytoin • Phenytoin^#

Carboxamides	Carbamazepine^# • Eslicarbazepine acetate • Oxcarbazepine • Oxitriptyline • Rufinamide

Primarily calcium


Succinimides	Ethosuximide^# • Mesuximide • Phensuximide

AMPA receptor

Perampanel

Unknown/ungrouped

Phenyltriazine (Lamotrigine), Oxazolidinediones (Ethadione • Paramethadione • Trimethadione), Ureas (Phenacemide • Pheneturide), Monosaccharide (Topiramate)

Channel openers

Potassium	Retigabine

Indirect GABA agents

Carboxylic acids/ Fatty acid derivatives	GABA transaminase inhibitor: Valproic acid^# (Sodium valproate & Valproate semisodium) • Valpromide • Valnoctamide • Valproate pivoxil GABA reuptake inhibitor: Tiagabine

GABA analogs	Gabapentin • Pregabalin • Progabide • Tolgabide • Vigabatrin

Unknown/multiple/
unsorted


Carbamates	Emylcamate • Felbamate • Meprobamate • Carisbamate

Pyrrolidines	Brivaracetam • Levetiracetam • Nefiracetam • Seletracetam

Propionates	Beclamide • Lacosamide

Aldehydes	Paraldehyde

Bromides	Potassium bromide • Sodium bromide

^#WHO-EM. ^‡Withdrawn from market. Clinical trials: ^†Phase III. ^§Never to phase III

M: CNS

anat(n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp

noco(m/d/e/h/v/s)/cong/tumr, sysi/epon, injr

proc, drug(N1A/2AB/C/3/4/7A/B/C/D)

GABAergics

Receptor
ligands

GABA_A	Agonists: Main site: Bamaluzole • Gaboxadol • Ibotenic acid • Isoguvacine • Isonipecotic acid • Muscimol (Amanita Muscaria) • Progabide • SL 75102 • Thiomuscimol • Tolgabide; Positive allosteric modulators: Barbiturates • Benzodiazepines • Carbamates • Chlormezanone • Clomethiazole • Ethanol (Alcohol) • Etomidate • Kavalactones (Kava) • Loreclezole • Metomidate • Neuroactive steroids • Nonbenzodiazepines (β-Carbolines, Cyclopyrrolones, Imidazopyridines, Pyrazolopyrimidines, etc.) • Phenols • Piperidinediones • Propanidid • Pyrazolopyridines • Quinazolinones • ROD-188 • Skullcap • Stiripentol • Valerenic acid (Valerian) * See Template:GABAAergics for a full list of GABA_A positive allosteric modulators. Antagonists: Main site: Bicuculline • Gabazine • Pitrazepin • Quisqualamine; Negative allosteric modulators: α5IA • Bilobalide • Cicutoxin • Cyclothiazide • DMCM • Flumazenil • Flurothyl • Furosemide • L-655,708 • Oenanthotoxin • Penicillin • Pentylenetetrazol • Picrotoxin • PWZ-029 • Ro15-4513 • Sarmazenil • Suritozole • Thujone (Absinthe) • Thiocolchicoside • ZK-93426

GABA_B	Agonists: Main site: 1,4-Butanediol • Baclofen • GBL • GHB • GHV • GVL • Lesogaberan • Phenibut • Progabide • SKF-97,541 • Tolgabide; Positive allosteric modulators: BHF-177 • BHFF • BSPP • CGP-7930 • GS-39783 Antagonists: Main site: CGP-35348 • Phaclofen • Saclofen • SCH-50911

GABA_C	Agonists: Main site: CACA • CAMP • GABOB • N(4)-chloroacetylcytosine arabinoside • Progabide • Tolgabide Antagonists: Main site: Bilobalide • TPMPA

Reuptake
inhibitors

Plasmalemmal

GAT inhibitors	CI-966 • Deramciclane • EF-1502 • Gabaculine • Guvacine • Nipecotic acid • NNC 05-2090 • SKF-89976A • SNAP-5114 • Tiagabine

Enzyme
inhibitors

Anabolism

GAD inhibitors	Allylglycine

Catabolism

GABA-T inhibitors	3-Hydrazinopropionic acid • Aminooxyacetic acid • Gabaculine • Isoniazid • Phenelzine • Phenylethylidenehydrazine • Sodium valproate • Valnoctamide • Valproate pivoxil • Valproate semisodium (Divalproex sodium) • Valproic acid • Valpromide • Vigabatrin

Others

Precursors	Glutamate • Glutamine

Cofactors	Vitamin B6 (pyridoxine, pyridoxamine, pyridoxal phosphate)

Others	Gabapentin • L-Theanine • Picamilon • Pregabalin

GABA_A receptor PAMs

Barbiturates	Allobarbital • Alphenal • Amobarbital • Aprobarbital • Barbexaclone • Barbital • Benzobarbital • Benzylbutylbarbiturate • Brallobarbital • Brophebarbital • Bucolome • Butabarbital • Butalbital • Butobarbital • Butallylonal • Carbubarb • Crotylbarbital • Cyclobarbital • Cyclopal • Difebarbamate • Enallylpropymal • Ethallobarbital • Febarbamate • Heptabarb • Heptobarbital • Hexethal • Hexobarbital • Metharbital • Methohexital • Methylphenobarbital • Narcobarbital • Nealbarbital • Pentobarbital • Phenobarbital • Phetharbital • Primidone • Prazitone • Probarbital • Propallylonal • Proxibarbal • Proxibarbital • Reposal • Secbutabarbital • Secobarbital • Sigmodal • Spirobarbital • Talbutal • Tetrabamate • Tetrabarbital • Thialbarbital • Thiamylal • Thiobarbital • Thiobutabarbital • Thiopental • Valofane • Vinbarbital • Vinylbital

Benzodiazepines	Adinazolam • Alprazolam • Arfendazam • Avizafone • Bentazepam • Bretazenil • Bromazepam • Brotizolam • Camazepam • Chlordiazepoxide • Ciclotizolam • Cinolazepam • Clazolam • Climazolam • Clobazam • Clonazepam • Clorazepate • Clotiazepam • Cloxazolam • Cyprazepam • Delorazepam • Diazepam • Doxefazepam • Elfazepam • Estazolam • Ethyl carfluzepate • Ethyl dirazepate • Ethyl loflazepate • Etizolam • Fletazepam • Fludiazepam • Flunitrazepam • Flurazepam • Flutazolam • Flutemazepam • Flutoprazepam • Fosazepam • Gidazepam • Girisopam • Halazepam • Haloxazolam • Iclazepam • Imidazenil • Ketazolam • Lofendazam • Lopirazepam • Lopirazepam • Loprazolam • Lorazepam • Lormetazepam • Meclonazepam • Medazepam • Menitrazepam • Metaclazepam • Mexazolam • Midazolam • Nerisopam • Nimetazepam • Nitrazepam • Nitrazepate • Nordazepam • Oxazepam • Oxazolam • Phenazepam • Pinazepam • Pivoxazepam • Prazepam • Premazepam • Proflazepam • QH-II-66 • Quazepam • Reclazepam • Remimazolam • Rilmazafone • Ripazepam • Ro48-6791 • SH-053-R-CH3-2′F • Sulazepam • Temazepam • Tetrazepam • Tofisopam • Triazolam • Triflubazam • Uldazepam • Zapizolam • Zolazepam • Zomebazam

Carbamates	Carisbamate • Carisoprodol • Cyclarbamate • Difebarbamate • Emylcamate • Ethinamate • Febarbamate • Felbamate • Hexapropymate • Lorbamate • Mebutamate • Meprobamate • Methocarbamol • Nisobamate • Pentabamate • Phenprobamate • Procymate • Styramate • Tetrabamate • Tybamate

Neuroactive steroids	Acebrochol • Allopregnanolone • Alphadolone • Alphaxolone • Ganaxolone • Hydroxydione • Minaxolone • Org 20599 • THDOC

Nonbenzodiazepines	β-Carbolines: Abecarnil • Gedocarnil • SL-651,498 • ZK-93423; Cyclopyrrolones: Eszopiclone • Pagoclone • Pazinaclone • Suproclone • Suriclone • Zopiclone; Imidazopyridines: Alpidem • Necopidem • Saripidem • Zolpidem; Pyrazolopyrimidines: Divaplon • Fasiplon • Indiplon • Lorediplon • Ocinaplon • Panadiplon • Taniplon • Zaleplon; Others: Adipiplon • CGS-8216 • CGS-9896 • CGS-13767 • CGS-20625 • CL-218,872 • CP-615,003 • ELB-139 • GBLD-345 • L-838,417 • NS-2664 • NS-2710 • NS-11394 • Pipequaline • ROD-188 • RWJ-51204 • SB-205,384 • SX-3228 • TP-003 • TPA-023 • TP-13 • U-89843A • U-90042 • Y-23684

Phenols	Fospropofol • Propofol • Thymol

Piperidinediones	Glutethimide • Methyprylon • Piperidione • Pyrithyldione

Pyrazolopyridines	Cartazolate • Etazolate • ICI-190,622 • Tracazolate

Quinazolinones	Afloqualone • Cloroqualone • Diproqualone • Etaqualone • Mebroqualone • Mecloqualone • Methaqualone • Methylmethaqualone

Volatiles/gases	2-Methyl-2-butanol • Acetone • Acetophenone • Acetylglycinamide chloral hydrate • Benzene • Butane • Butanol • Butylene • Centalun • Chloral • Chloral hydrate • Chlorobutanol • Chloroform • Cyclopropane • Desflurane • Dichloromethane • Diethyl ether • Enflurane • Ethanol (Alcohol) • Ethyl chloride • Ethylene • Gasoline • Halothane • Isoflurane • Kerosine • Menthol • Methanol • Methoxyflurane • Methoxypropane • Methylbutanol • Nitric oxide • Nitrogen • Nitrous oxide • Paraldehyde • Pentanol • Propane • Propanol • Propylene • Sevoflurane • Toluene • Trichloroethanol • Trichloroethylene • Vinyl ether • Xenon

Others	Bromide (Lithium bromide, Potassium bromide, Sodium bromide) • Chloralodol • Chloralose • Chlormezanone • Clomethiazole • DEABL • Etazepine • Ethchlorvynol • Etifoxine • Etomidate • GABA • Kavalactones (Kava) • Loreclezole • Methylpentynol • Metomidate • Org 25,435 • Petrichloral • Propanidid • Skullcap • Stiripentol • Sulfonmethane • Tetronal • Triclofos • Trional • Valeric acid, Valerenic acid (Valerian)