NSI-189 (also known as Amdiglurax, ALTO-100, ALTO-300)

Safety Summary

In clinical trials (Phase 1B: PMID 26643541; Phase 2: PMID 30626911; PMC7303010), NSI-189 phosphate was generally well tolerated at doses of 40-120 mg/day. No treatment-related serious adverse events (SAEs) were reported in any trial. No dose-limiting toxicities were identified. Discontinuation rates in the Phase 2 trial were lower in the NSI-189 groups than placebo. Complete adverse event frequency tables by dose cohort were not published in the publicly available manuscripts. No abuse potential has been reported (DrugBank DB16230; Wikipedia). No anti-drug antibody formation or immunogenicity concerns exist (NSI-189 is a small molecule, not a biologic). Community reports (ANECDOTAL) consistently cite anxiety as the most common adverse effect, along with paresthesia, headaches, and depersonalization, particularly during early dosing or at higher doses. These effects often abate with dose reduction or cycling. No formal drug-drug interaction data (CYP inhibition/induction, transporter effects) has been published (DrugBank DB16230). Long-term safety data beyond 12 weeks is not available from controlled clinical studies; no tolerance, withdrawal, or carcinogenicity signals have been reported in the available data.