A randomized, double-blind, placebo controlled, phase 1 study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of LB-102, a selective dopamine D/5-HT inhibitor.

LB-102 is an N-methylated analogue of amisulpride under development to treat schizophrenia. LB-102 was evaluated in a Phase 1, double-blind, placebo-controlled, clinical study to evaluate safety and pharmacokinetics. This was a first-in-human study examining single and multiple doses of LB-102 administered orally in 64 healthy volunteers.

Antipsychotic Benzamides Amisulpride and LB-102 Display Polypharmacy as Racemates, Enantiomers Engage Receptors D and D, while Enantiomers Engage 5-HT.

Benzamide antipsychotics such as amisulpride are dosed as racemates though efficacy is assumed to be mediated through enantiomer binding to D receptors. At prescribed doses, the benzamides likely display polypharmacy since brain exposure should be sufficient to engage the 5-HT receptors, as well. Curiously, the studies herein reveal that racemic dosing is required to engage both targets since the D receptor has an almost 40-fold selectivity for the enantiomer, while the 5-HT receptor has greater than 50-fold preference for the enantiomer.

Fosmetpantotenate (RE-024), a phosphopantothenate replacement therapy for pantothenate kinase-associated neurodegeneration: Mechanism of action and efficacy in nonclinical models.

In cells, phosphorylation of pantothenic acid to generate phosphopantothenic acid by the pantothenate kinase enzymes is the first step in coenzyme A synthesis. Pantothenate kinase 2, the isoform localized in neuronal cell mitochondria, is dysfunctional in patients with pantothenate kinase-associated neurodegeneration. Fosmetpantotenate is a phosphopantothenic acid prodrug in clinical development for treatment of pantothenate kinase-associated neurodegeneration, which aims to replenish phosphopantothenic acid in patients.

An examination of the purported reverse anomeric effect beyond acetylated N-xylosyl- and N-glucosylimidazoles.

Syntheses of six new N-(pentopyranosyl)imidazoles have been achieved, and their conformations were observed with and without protonation. A decisive decrease in J(5',4), consistent with stabilization of the 1C4 conformations, was clearly observed for three N-(pentopyranosyl)imidazoles. As well, no reverse anomeric stabilization was observed for N-(2,3,4-tri-O-acetyl-alpha-D-lyxopyranosyl)imidazole upon protonation.