A new version of Amisulpride is in phase 1 trials in the USA. It will be the best medication to come in the US for schizophrenia:
Amisulpride: What’s Old Can Be New in the United States | Psychiatric News (psychiatryonline.org)
Modified Amisulpride Being Studied
In 2014, Grattan and Prensky connected to discuss ideas for how to bring amisulpride to the United States. Their initial thought was to designate amisulpride as an orphan drug for ultra-resistant schizophrenia, given its ability to augment clozapine. (An orphan drug designation provides benefits like tax incentives for groups willing to sponsor a treatment for a rare disorder.)
That idea did not pan out, but working with chemist Andrew Vaino, Ph.D., chief science officer for LB, the pair devised a strategy for chemically enhancing the amisulpride molecule, and LB was born.
“One shortcoming of amisulpride is that the molecule does not get into the brain that easily,” Prensky said, which necessitates oral doses as high as 800 mg a day. (As a comparison, the typical doses for the commonly used antipsychotics olanzapine or risperidone are about 6 mg to 20 mg a day.)
Adding a small chemical tag to amisulpride to make it more fat soluble would enable it to pass the blood-brain barrier more easily, allowing doses of the medication (and potential side effects from these doses) to be reduced.
LB recently completed its phase 1a safety study of its methylated amisulpride (named LB-102) in healthy volunteers and found that the drug was well tolerated up to 150 mg a day. This is well above the effective dose for most patients, which is believed to be between 25 mg to 75 mg a day based on an ongoing PET scan study looking at how the drug binds to brain receptors. Prensky said LB is preparing to launch its phase 2 study this year and hopes to recruit at least 300 participants with schizophrenia.
“It’s still early in the process, but we are hop-skipping along nicely,” Prensky said. He pointed out that the FDA approved an intravenous formulation of amisulpride in 2020 to treat post-operative nausea and vomiting. That medication only uses 5 mg of amisulpride, but Prensky said the approval did provide some guideposts as to what concerns the FDA has in relation to amisulpride.
“In addition, we have also gotten some of the top schizophrenia scientists in the country on our scientific board to point us in the right direction,” he added. “When luminaries like John Kane, Cristoph Correll, and Ira Glick were willing to join us in the earliest days, it shows that the psychiatric community wants this drug in the United States.” ■
“Amisulpride, Aripiprazole, and Olanzapine in Patients With Schizophrenia-Spectrum Disorders (BeSt InTro): A Pragmatic, Rater-Blind, Semi-Randomised Trial” is posted here.
“Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1)” is posted here.
“Effectiveness of Antipsychotic Drugs in First-Episode Schizophrenia and Schizophreniform Disorder: An Open Randomised Clinical Trial” is posted here.
ISSUES
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Nick Zagorski, Psychiatric News, 2020
Stefan Leucht et al., American Journal of Psychiatry, 2009
Robert A. Rosenheck, Psychiatric Services, 2005
Beatriz H. Grecco et al., Journal of Intensive Medicine, 2022
Chen Rui et al., Acta Physica Sinica, 2021
Weiqin Wang et al., Journal of Intensive Medicine, 2022