GALANTAMINE-MEMANTINE COMBINATION REGULATING THE KYNURENINE PATHWAY METABOLISM IN THE TREATMENT OF POST-STROKE DEPRESSION AND POST-STROKE COGNITIVE IMPAIRMENTS AND PREVENTION OF STROKE

Stroke is currently a leading cause of mortality and disability worldwide, often resulting in debilitating neuropsychiatric sequelae, such as poststroke depression (PSD) and poststroke cognitive impairments (PSCI). Despite advances in acute stroke care, effective therapeutic options for these complications and their effect on functional recovery and quality of life remain limited as there are no FDA-approved treatments for PSD and PSCI. The kynurenine pathway (KP), the principal route of tryptophan metabolism, is a promising target for novel therapeutic strategies. KP produces metabolites, such as kynurenine, 3-hydroxykynurenine, and quinolinic acid, which act with various effects on neuroinflammation, excitotoxicity, and neuroplasticity. Disruption of KP has been increasingly implicated in the pathophysiology of both stroke and its neuropsychiatric aftermath. Factors leading to stroke enhance the activity of KP, leading to imbalances between neuroprotective and neurotoxic metabolites which cause cognitive impairments and diversion of tryptophan metabolism away from serotonin. Medications which target KP, such as galantamine and memantine, can work synergistically to restore balance between KP metabolites, reducing recurrent stroke risk in addition to mitigating PSD and PSCI. This review aims to elucidate the role of modulation of KP in stroke survivors, specifically with the galantamine-memantine combination, highlighting evidence and therapeutic prospects in prevention of stroke and its neuropsychiatric sequelae.