A systematic review of the toxicity of salsolinol and its metabolites

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a tetrahydroisoquinoline compound formed by the condensation reaction between dopamine and acetaldehyde. While it plays a role in normal physiological functions at physiological levels, elevated concentrations have been associated with toxicity. This study aimed to investigate the mechanisms underlying salsolinol toxicity. A literature search was conducted using PubMed and Scopus databases covering the years 2013 to 2023. A total of 6,678 studies were identified using predefined keywords such as "salsolinol," "tetrahydroisoquinoline," "DMDHIQ+," "N-methyl salsolinol," "toxicity," "toxic," and "toxin." Based on predetermined inclusion and exclusion criteria, 6,381 articles were excluded. Seven articles met the eligibility criteria and were critically appraised; all were included in this review. Most of the studies reviewed found that elevated levels of salsolinol in the blood and brain contributed to addiction-like behaviours, particularly in alcoholism, through enhanced dopaminergic signalling in the ventral tegmental area. Two studies examined the oxidative stress effects of salsolinol and its metabolites on neurons and their potential role in cancer development. A novel finding also implicated salsolinol in the degeneration of myenteric neurons, leading to alterations in gut function. Salsolinol and its metabolites exhibit toxic effects in both the central and peripheral nervous systems, primarily through oxidative stress and the modulation of addiction-related pathways. These findings underscore the need for further research to explore potential therapeutic targets to mitigate these pathological effects.