N-Methylamisulpride

N-Methylamisulpride (developmental code name LB-102) is a dopamine D₂ and D₃ receptor antagonist and serotonin 5-HT_2B and 5-HT₇ receptor antagonist which is under development for the treatment of schizophrenia.^{[1][2][3][4][5]} It is a benzamide derivative and is the N-methylated analogue of amisulpride.^[1][2] The drug is being developed for use both orally and parenterally.^[1]

N-Methylamisulpride

Clinical data
Other names	N-Methyl amisulpride; N′-Methylamisulpride; LB-102; LB102; LB-102-LAI
Drug class	Dopamine D2 and D3 receptor antagonist; Serotonin 5-HT2B and 5-HT7 receptor antagonist
Identifiers
IUPAC name N-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-2-methoxy-4-(methylamino)benzamide
CAS Number	2227154-23-4
PubChem CID	134542980
DrugBank	DB19214
ChemSpider	81367337
UNII	N81WKW91XF
ChEMBL	ChEMBL4594422
Chemical and physical data
Formula	C18H29N3O4S
Molar mass	383.51 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCN1CCCC1CNC(=O)C2=CC(=C(C=C2OC)NC)S(=O)(=O)CC
InChI InChI=1S/C18H29N3O4S/c1-5-21-9-7-8-13(21)12-20-18(22)14-10-17(26(23,24)6-2)15(19-3)11-16(14)25-4/h10-11,13,19H,5-9,12H2,1-4H3,(H,20,22) Key:NXKXZXNNWRYXRE-UHFFFAOYSA-N

Amisulpride exhibits low passive diffusion through the blood–brain barrier and this requires higher doses for central nervous system activity.^[2] N-Methylamisulpride has enhanced lipophilicity and hence improved passive diffusion through biological membranes like the blood–brain barrier compared to amisulpride.^[2] This in turn is expected to provide a higher ratio of brain to peripheral concentrations.^[2] The drug otherwise has similar pharmacodynamics and pharmacokinetics relative to amisulpride.^[2][5]

N-Methylamisulpride appears to have considerably greater clinical potency compared to amisulpride owing to its improved lipophilicity and blood–brain barrier permeability.^[2] A dosage of 50 mg/day N-methylamisulpride has been found to achieve 60 to 80% occupancy of the dopamine D₂ receptor, whereas 300 to 400 mg/day amisulpride achieved around 70% occupancy and doses of 630 to 910 mg/day amisulpride achieved 70 to 80% occupancy of the receptor.^[4][6]

Amisulpride has been associated with QT prolongation.^[7][8][9] Due to its greater ratio of brain to peripheral concentrations and much lower doses, N-methylamisulpride is expected to have reduced risk of QT prolongation in comparison.^[9][4]

As of December 2023, N-methylamisulpride is in phase 2 clinical trials for schizophrenia.^[1] It is being developed by LB Pharmaceuticals.^[1]

See also

• SEP-4199 (non-racemic amisulpride)