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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 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.[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 2clinical trials for schizophrenia.[1] It is being developed by LB Pharmaceuticals.[1]
^ abcdefgWu J, Kwan AT, Rhee TG, Ho R, d'Andrea G, Martinotti G, Teopiz KM, Ceban F, McIntyre RS (2023). "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. doi:10.1080/17512433.2023.2274538. PMID37864424.
^Biernat L, Grattan VT, Hixon MS, Prensky Z, Vaino AR (September 2022). "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. doi:10.1007/s00213-022-06185-7. PMID35841422.
^ abcWong 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 (October 2024). "PET clinical study of novel antipsychotic LB-102 demonstrates unexpectedly prolonged dopamine receptor target engagement". Neuropsychopharmacology. doi:10.1038/s41386-024-01951-x. PMID39414986.
^Martinot JL, Paillère-Martinot ML, Poirier MF, Dao-Castellana MH, Loc'h C, Mazière B (March 1996). "In vivo characteristics of dopamine D2 receptor occupancy by amisulpride in schizophrenia". Psychopharmacology (Berl). 124 (1–2): 154–158. doi:10.1007/BF02245616. PMID8935811.
^Smith RC, Leucht S, Davis JM (February 2019). "Maximizing response to first-line antipsychotics in schizophrenia: a review focused on finding from meta-analysis". Psychopharmacology (Berl). 236 (2): 545–559. doi:10.1007/s00213-018-5133-z. PMID30506237.
^Bordet C, Garcia P, Salvo F, Touafchia A, Galinier M, Sommet A, Montastruc F (January 2023). "Antipsychotics and risk of QT prolongation: a pharmacovigilance study". Psychopharmacology (Berl). 240 (1): 199–202. doi:10.1007/s00213-022-06293-4. PMID36515735.
^ abPrice, Lawrence H. (3 April 2023). "Data‐based decisions about antipsychotics and QT prolongation". The Brown University Psychopharmacology Update. 34 (5). Wiley: 7–8. doi:10.1002/pu.31012. ISSN1068-5308.