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**BMS-986368 + itraconazole** is an investigational combination of two drugs: BMS-986368, an orally administered dual inhibitor of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGLL), and itraconazole, a clinically approved antifungal agent. BMS-986368 is designed to increase endogenous endocannabinoid levels by blocking their breakdown, which may provide therapeutic effects in neurological diseases such as muscle spasticity associated with multiple sclerosis (MS), agitation in Alzheimer's disease, and epilepsy. The rationale for combining BMS-986368 with itraconazole is not established in clinical literature as of now. BMS-986368 is developed by Bristol Myers Squibb (originated from Celgene), is being studied in Phase 2 clinical trials for MS spasticity and agitation in Alzheimer's, and in Phase 1 for epilepsy. Itraconazole is a marketed antifungal agent that inhibits ergosterol biosynthesis and has been evaluated for off-label applications, but no published trials support its combination with BMS-986368 for neurological disorders.\nMechanistically, BMS-986368 works by inhibiting FAAH and MGLL, enzymes responsible for the degradation of endocannabinoids, resulting in increased signaling through cannabinoid pathways, which is thought to reduce spasticity and agitation. Itraconazole works by inhibiting fungal cytochrome P450 enzyme 14α-demethylase.\nNo direct evidence or clinical rationale for this specific combination was identified in available sources.
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