N-Methylamisulpride Explained

Drug Name:N-Methylamisulpride
Class:Dopamine D2 and D3 receptor antagonist; Serotonin 5-HT2B and 5-HT7 receptor antagonist
Cas Number:2227154-23-4
Pubchem:134542980
Drugbank:DB19214
Chemspiderid:81367337
Unii:N81WKW91XF
Chembl:4594422
Synonyms:N-Methyl amisulpride; N′-Methylamisulpride; LB-102; LB102; LB-102-LAI
Iupac Name:N-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-2-methoxy-4-(methylamino)benzamide
C:18
H:29
N:3
O:4
S:1
Smiles:CCN1CCCC1CNC(=O)C2=CC(=C(C=C2OC)NC)S(=O)(=O)CC
Stdinchi: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)
Stdinchikey:NXKXZXNNWRYXRE-UHFFFAOYSA-N

N-Methylamisulpride (developmental code name LB-102) is a dopamine D2 and D3 receptor antagonist and serotonin 5-HT2B 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. The drug is being developed for use both orally and parenterally.

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

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

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

See also

Notes and References

  1. Web site: N-methyl amisulpride . AdisInsight . 26 December 2023 . 22 October 2024.
  2. Wu J, Kwan AT, Rhee TG, Ho R, d'Andrea G, Martinotti G, Teopiz KM, Ceban F, McIntyre RS . A narrative review of non-racemic amisulpride (SEP-4199) for treatment of depressive symptoms in bipolar disorder and LB-102 for treatment of schizophrenia . Expert Rev Clin Pharmacol . 16 . 11 . 1085–1092 . 2023 . 37864424 . 10.1080/17512433.2023.2274538 .
  3. Biernat L, Grattan VT, Hixon MS, Prensky Z, Vaino AR . A randomized, double-blind, placebo controlled, phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of LB-102, a selective dopamine D2/3/5-HT7 inhibitor . Psychopharmacology (Berl) . 239 . 9 . 3009–3018 . September 2022 . 35841422 . 10.1007/s00213-022-06185-7 .
  4. Wong DF, Chand GB, Caito N, Eramo A, Grattan VT, Hixon MS, Nicol G, Lessie E, Prensky Z, Kuwabara H, Tian L, Valenta I, Schindler TH, Gründer G, Vaino AR . PET clinical study of novel antipsychotic LB-102 demonstrates unexpectedly prolonged dopamine receptor target engagement . Neuropsychopharmacology . October 2024 . 39414986 . 10.1038/s41386-024-01951-x . free .
  5. Grattan V, Vaino AR, Prensky Z, Hixon MS . Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, S Enantiomers Engage Receptors D2 and D3, while R Enantiomers Engage 5-HT7 . ACS Omega . 4 . 9 . 14151–14154 . August 2019 . 31497735 . 6714530 . 10.1021/acsomega.9b02144 .
  6. Martinot JL, Paillère-Martinot ML, Poirier MF, Dao-Castellana MH, Loc'h C, Mazière B . In vivo characteristics of dopamine D2 receptor occupancy by amisulpride in schizophrenia . Psychopharmacology (Berl) . 124 . 1–2 . 154–158 . March 1996 . 8935811 . 10.1007/BF02245616 .
  7. Smith RC, Leucht S, Davis JM . Maximizing response to first-line antipsychotics in schizophrenia: a review focused on finding from meta-analysis . Psychopharmacology (Berl) . 236 . 2 . 545–559 . February 2019 . 30506237 . 10.1007/s00213-018-5133-z .
  8. Bordet C, Garcia P, Salvo F, Touafchia A, Galinier M, Sommet A, Montastruc F . Antipsychotics and risk of QT prolongation: a pharmacovigilance study . Psychopharmacology (Berl) . 240 . 1 . 199–202 . January 2023 . 36515735 . 10.1007/s00213-022-06293-4 .
  9. Price . Lawrence H. . Data-based decisions about antipsychotics and QT prolongation . The Brown University Psychopharmacology Update . Wiley . 34 . 5 . 3 April 2023 . 1068-5308 . 10.1002/pu.31012 . 7–8.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "N-Methylamisulpride".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2025, A B Cryer, All Rights Reserved. Cookie policy.