Plasma and Urine Salsolinol in Humans: Effect of Acute Ethanol Intake on the Enantiomeric Composition of Salsolinol

Abstract

The tetrahydroisoquinoline (TIQ) salsolinol (SAL), a condensation product of dopamine and pyruvate or acetaldehyde, is one of the neuropharmacologically active alkaloids in mammals. Previous HPLC studies have shown that the R-enantiomer of SAL is largely predominant, or is the only enantiomer in the urine of healthy subjects, whereas the S-enantiomer was found predominant in the urine of alcoholics. An enzymatic pathway for SAL formation that is influenced by chronic alcohol intake was proposed. However, our analyses showed that the SAL detectable in human urine and plasma is racemic, at least in healthy subjects. No change of the enantiomeric distribution was observed after an acute alcohol ingestion (1 g alcohol/kg body weight). Using a new method for the resolution of the SAL enantiomers and gas chromatography mass spectrometry analysis, the SAL enantiomers were quantified in the urine and plasma of 24 subjects before and after the intake of alcohol. Special dietary conditions were observed to avoid interferences by the SAL of the foodstuff. Although the distribution of SAL enantiomers was not changed after alcohol intake, the total urinary SAL output and the plasma concentration of SAL were significantly influenced in different ways. Only five subjects showed a significant increase both in plasma SAL concentration and in the total urinary SAL output, whereas 19 subjects showed decreased or unchanged SAL levels after alcohol administration. Data also show that only the subjects with low baseline levels (mean of 0.148 ng SAL/ml plasma) tend to increase SAL levels after ethanol ingestion, which may imply some genetic basis for the response.

Salsolinol Stimulates Dopamine Neurons in Slices of Posterior Ventral Tegmental Area Indirectly by Activating μ-Opioid Receptors

“…It has been suggested that salsolinol has a role in the etiology of alcoholism (Davis and Walsh, 1970). Except for the work of Haber et al (1996), previous studies on humans found that after acute (Faraj et al, 1989;Rommelspacher et al, 1995) or chronic (Faraj et al, 1989) alcohol drinking salsolinol levels in plasma (and presumably brain) may increase. Indeed, forced chronic ethanol consumption raised salsolinol levels in various brain regions of animals as confirmed by Starkey et al (2006) and Rojkovicova et al (2008), who showed that the pattern of ethanol intake determines how much salsolinol levels in the brain are enhanced.…”

“…Accumulating evidence suggests that some of the acute rewarding effects of ethanol are produced by its metabolites, such as salsolinol (Deng and Deitrich, 2008). In the brains of mammals racemic (R and S) salsolinol is formed by nonenzymatic Pictet-Spengler condensation of dopamine with acetaldehyde (Rommelspacher et al, 1995;Haber et al, 1996), the main metabolite of ethanol. It has been suggested that salsolinol has a role in the etiology of alcoholism (Davis and Walsh, 1970).…”

Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

“…Sal is a kind of catechol isoquinoline that can be found in brain, cerebrospinal fluid, blood, and urine (Haber et al 1996). It can also be detected in some foods and beverages, such as dried banana and port wine, suggesting that consumption of such daily food items can affect Sal level in tissues (Smythe et al 1985).…”

Fast liquid chromatography separation and multiple‐reaction monitoring mass spectrometric detection of neurotransmitters

“…It is thought that some metabolites of salsolinol are involved in the etiopathogenesis of Parkinson's disease [11,12]. In addition, it is believed that salsolinol is implicated in alcohol addiction [13].…”