Sembragiline WikiZero

Sembragiline
Clinical data

Other names	EVT-302; EVT302; RG-1577; RG1577; RO-4602522; RO4602522
Routes of administration	Oral^[1]
Drug class	Reversible monoamine oxidase B (MAO-B) inhibitor
Identifiers
IUPAC name N-[(3S)-1-[4-[(3-fluorophenyl)methoxy]phenyl]-5-oxopyrrolidin-3-yl]acetamide
CAS Number	676479-06-4
PubChem CID	10246762
ChemSpider	8422249
UNII	K3W9672PNJ
KEGG	D11224
ChEMBL	ChEMBL3707394
Chemical and physical data
Formula	C₁₉H₁₉FN₂O₃
Molar mass	342.370 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC(=O)N[C@H]1CC(=O)N(C1)C2=CC=C(C=C2)OCC3=CC(=CC=C3)F
InChI InChI=1S/C19H19FN2O3/c1-13(23)21-16-10-19(24)22(11-16)17-5-7-18(8-6-17)25-12-14-3-2-4-15(20)9-14/h2-9,16H,10-12H2,1H3,(H,21,23)/t16-/m0/s1 Key:VMAVCCUQTALHOB-INIZCTEOSA-N

Sembragiline (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name; developmental code names EVT-302, RG-1577, RO-4602522) is a selective and reversible monoamine oxidase B (MAO-B) inhibitor which is or was under development for the treatment of Alzheimer's disease.^[1]^[2]^[3]^[4] It was also under development for the treatment of smoking withdrawal, but development for this indication was discontinued.^[1]^[2]^[3] The drug is taken by mouth.^[1]^[4] Sembragiline is or was being developed by Roche and Evotec SE.^[1]^[2]^[3]

References

[edit]

^ ^a ^b ^c ^d ^e "Sembragiline". AdisInsight. 5 November 2023. Retrieved 24 February 2025.
^ ^a ^b ^c "Delving into the Latest Updates on Sembragiline with Synapse". Synapse. 22 February 2025. Retrieved 24 February 2025.
^ ^a ^b ^c "Sembragiline". ALZFORUM. 20 November 2015. Retrieved 24 February 2025.
^ ^a ^b Lin P, Sun J, Cheng Q, Yang Y, Cordato D, Gao J (December 2021). "The Development of Pharmacological Therapies for Alzheimer's Disease". Neurology and Therapy. 10 (2): 609–626. doi:10.1007/s40120-021-00282-z. PMC 8571471. PMID 34532845. Sembragiline (also known as RO4602522, RG1577 and EVT302) is a potent, selective and reversible monoamine oxidase B (MAO-B) inhibitor developed to treat AD. A PET study revealed almost complete inhibition of central MAO-B at an oral dose of 1 mg per day in AD patients; however, no cognitive benefits were detected after treatment [91].

Monoamine metabolism modulators

Non-specific

AAAD

Substrates→Products: L-DOPA (levodopa)→Dopamine
5-HTP→Serotonin
L-Histidine→Histamine
Phenylalanine→Phenethylamine
L-Tyrosine→Tyramine
Tryptophan→Tryptamine

MAO

Substrates→Products (with ALDHTooltip Aldehyde dehydrogenase/ALRTooltip ALR): Epinephrine (adrenaline)→DHMA Metanephrine→MHPG/VMA Norepinephrine (noradrenaline)→DHMA Normetanephrine→MHPG/VMA Dopamine→DOPAC 3-Methoxytyramine→HVA Serotonin→5-HIAA Inhibitors: Non-selective: Benmoxin Caroxazone Echinopsidine Furazolidone Guineesine Hydralazine Indantadol Iproclozide Iproniazid Isocarboxazid Isoniazid Linezolid Mebanazine Metfendrazine Nialamide Octamoxin Paraxazone Phenelzine Pheniprazine Phenoxypropazine Pivhydrazine Procarbazine Safrazine Tranylcypromine
Inhibitors: MAO-A-selective: Amiflamine Bazinaprine Befloxatone Brofaromine Cimoxatone Clorgiline CX157 (Tyrima) Eprobemide Esuprone Harmala alkaloids (e.g., harmine, harmaline, harman, norharman, tetrahydroharmine) Methylene blue Metralindole Minaprine Moclobemide Pirlindole Sercloremine Tetrindole Toloxatone
Inhibitors: MAO-B selective: Adarigiline Almoxatone D-Deprenyl Desmethylselegiline Ethanol Ladostigil Lazabemide Milacemide Mofegiline Nicotine Pargyline^‡ Rasagiline Safinamide Selegiline (L-Deprenyl) Sembragiline Tisolagiline Vafidemstat

Phenethylamines
(dopamine, epinephrine,
norepinephrine)

PAHTooltip Phenylalanine hydroxylase	Substrates→Products: Phenylalanine→Tyrosine Inhibitors: 3,4-Dihydroxystyrene α-Methylphenylalanine
THTooltip Tyrosine hydroxylase	Substrates→Products: Tyrosine→L-DOPA (levodopa) Inhibitors: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Iodotyrosine α-Methyl-5-hydroxytryptophan (α-Me-5-HTP) α-Methylphenylalanine Aquayamycin Bulbocapnine Methyldopa (α-methyl-L-DOPA) Metirosine (α-methyl-p-tyrosine) Oudenone
DBHTooltip Dopamine beta-hydroxylase	Substrates→Products: Dopamine→Norepinephrine (Noradrenaline) Inhibitors: Bupicomide Disulfiram Dopastin Etamicastat Fusaric acid Nepicastat Phenopicolinic acid Tropolone Zamicastat
PNMTTooltip Phenylethanolamine N-methyltransferase	Substrates→Products: Norepinephrine (noradrenaline)→Epinephrine (adrenaline) Inhibitors: CGS-19281A SKF-64139 SKF-7698
COMTTooltip Catechol-O-methyl transferase	Substrates→Products: Dopamine→3-Methoxytyramine DOPAC→Homovanillic acid Norepinephrine→Normetanephrine Epinephrine→Metanephrine DOPEG→MOPEG DOMA→VMA 2-Hydroxyestradiol→2-Methoxyestradiol 2-Hydroxyestrone→2-Methoxyestrone 4-Hydroxyestradiol→4-Methoxyestradiol 4-Hydroxyestrone→4-Methoxyestrone Inhibitors: 2-Hydroxyestradiol 2-Hydroxyestrone Entacapone Nebicapone Neluxicapone Nitecapone Opicapone Quinalizarin Tolcapone

Tryptamines
(serotonin, melatonin)

TPHTooltip Tryptophan hydroxylase	Substrates→Products: Tryptophan→5-HTP Inhibitors: AGN-2979 Fenclonine (PCPA) Telotristat ethyl
AANATTooltip Serotonin N-acetyl transferase	Substrates→Products: Serotonin→N-Acetylserotonin
ASMTTooltip Acetylserotonin O-methyltransferase	Substrates→Products: N-Acetylserotonin→Melatonin

Histamine

HDCTooltip Histidine decarboxylase	Substrates→Products: L-Histidine→Histamine Inhibitors: Catechin Alpha-Fluoromethylhistidine Histidine methyl ester Meciadanol Naringenin Tritoqualine
HNMTTooltip Histamine N-methyltransferase	Substrates→Products: Histamine→N-Methylhistamine Inhibitors: Amodiaquine Diphenhydramine Harmaline Metoprine Quinacrine SKF-91488 Tacrine
DAOTooltip Diamine oxidase	Substrates→Products: Histamine→Imidazole acetic acid Inhibitors: Pimagedine (aminoguanidine)

See also: Receptor/signaling modulators • Adrenergics • Dopaminergics • Melatonergics • Serotonergics • Monoamine reuptake inhibitors • Monoamine releasing agents • Monoamine neurotoxins

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