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For instance, metformin, is generally well-tolerated but can cause gastrointestinal side effects (e.g., nausea, diarrhea) and, in rare cases, lactic acidosis, particularly in patients with renal impairment [118]
Documented mechanisms of action Preclinical studies (mostly Russian, to be reproduced in international protocols) report several mechanistic targets: BDNF increase (Brain-Derived Neurotrophic Factor) in the hippocampus and frontal cortex, measured by ELISA and Western blot 24-72 h post-administration Monoaminergic system modulation : cortical dopamine increase, serotonergic modulation Activation of the melanocortin pathway via MC4R receptors (residue shared with ACTH) Anti-oxidant and anti-apoptotic effect in cerebral ischaemia models (MCAO, middle cerebral artery occlusion) Experimental paradigms The most reported rodent models are the Morris water maze (spatial memory), novel object recognition (recognition memory), passive avoidance (aversive learning)
