Disease relevance of C09642

• The results indicate that tetrahydroisoquinoline and salsolinol specifically affect the nigrostriatal dopamine system, but only when administered chronically, and thus are compatible with the view that endogenous tetrahydroisoquinolines may participate in pathogenesis of Parkinson's disease [1].
• The (R)- and (S)-enantiomers of salsolinol, the dopamine-derived tetrahydroisoquinolines, were found to inhibit the activity of tryptophan hydroxylase (TPH), prepared from serotonin-producing murine mastocytoma P-815 cells [2].
• 1-Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism [3].
• Insulin-like growth factor-1 protects human dopaminergic SH-SY5Y cells from salsolinol-induced toxicity [4].
• Among salsolinol analogs examined, only N-methyl-(R)- salsolinol (NM(R)Sal) induced behavioral changes very similar to those in Parkinson's disease: hypokinesia, stiff tail, limb twitching at rest and postural abnormality [5].

Psychiatry related information on C09642

• Increase in salsolinol level in the cerebrospinal fluid of parkinsonian patients is related to dementia: advantage of a new high-performance liquid chromatography methodology [6].
• In addition, the rewarding effect of salsolinol especially under psychological stress may involve the endogenous central opioid system, i.e., mu-opioid receptor [7].
• BACKGROUND: The formation of salsolinol (SAL) has been hypothesized to be a factor contributing to alcoholism and alcohol abuse [8].
• The enhanced salsolinol levels in patients with visual hallucinations seem to be due to an overloaded dopaminergic pathway with an imbalance between dopaminergic and serotonergic systems [9].
• We cannot confirm the reports that salsolinol or THP produce withdrawal symptoms when infused [10].

High impact information on C09642

• Differential cell death induced by salsolinol with and without copper: possible role of reactive oxygen species [11].
• The strong association of CSF salsolinol level with dementia, but not with L-dopa treatment suggests that salsolinol does not originate from L-dopa metabolism, and that its elevation is an indicator of neurodegenerative processes resulting in damage to brain areas mediating cognitive functions [6].
• We conclude that salsolinol is not responsible for PRL secretion induced by beer ingestion [12].
• Precocious hatching enzyme secretion from denuded zebrafish embryos is caused by salsolinol, whereas dopamine has an opposite effect [13].
• Determination of salsolinol and related catecholamines through on-line preconcentration and liquid chromatography/atmospheric pressure photoionization mass spectrometry [14].

Chemical compound and disease context of C09642

• In this study we sought to determine whether salsolinol-induced cytotoxicity in SH-SY5Y human neuroblastoma cells, a cloned cell line which expresses dopaminergic activity, could also be prevented by nicotine pretreatment, and if so, which nicotinic receptors may mediate the actions of nicotine [15].
• 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), an endogenous parkinsonism-preventing substance, and its 5-, 6-, and 7-hydroxylated derivatives are reported to show in vitro neuroprotective activity against toxicity due to salsolinol in SH-SY5Y human neuroblastoma cells [16].

Biological context of C09642

• Binding site of salsolinol: its properties in different regions of the brain and the pituitary gland of the rat [17].
• The inhibition of catecholamine uptake corresponded to the increase displacement of [3H]nisoxetine from the uptake 1 site by salsolinol, as the Ki (353 muM) for displacement was similar to the IC50 (411 and 379 muM) for uptake [18].
• Possible role of salsolinol quinone methide in the decrease of RCSN-3 cell survival [19].
• TRPC1 protects human SH-SY5Y cells against salsolinol-induced cytotoxicity by inhibiting apoptosis [20].
• These results suggest that salsolinol causes oxidative stress by decreasing the levels of GSH and by increasing ROS production, and these events may lead to the death of dopaminergic cell [21].

Anatomical context of C09642

• As it cannot cross the blood-brain barrier, salsolinol as the R enantiomer in the brain is considered to be synthesized in situ in dopaminergic neurons [22].
• The chronic ethanol administration produced a significant increase of salsolinol concentrations in dopamine-rich brain areas, e.g., the striatum and the limbic forebrain [23].
• We report that chronic administration of tetrahydroisoquinoline and salsolinol causes a decrease in a dopamine metabolism: the effect of tetrahydroisoquinoline was limited to the striatum, while salsolinol caused also a dramatic decline of dopamine level in the substantia nigra [1].
• Results are interpreted as supporting the hypothesis that salsolinol-like substances may mediate some of the effects of alcohol on the central nervous system [24].
• Product 2 was only poorly toxic to PC12 cells, whereas its methylated derivative 3 was as toxic as salsolinol, an established neurotoxin [25].

Associations of C09642 with other chemical compounds

• Effects of R and S enantiomers of salsolinol on kinetic properties of tyrosine hydroxylase [tyrosine, tetrahydrobiopterin:oxygen oxidoreductase (3-hydroxylating); EC 1.14.16.2], the rate-limiting enzyme of catecholamine biosynthesis, were examined [22].
• In vivo study of salsolinol produced by a high concentration of acetaldehyde in the striatum and nucleus accumbens of free-moving rats [26].
• In human caudate nucleus, the amounts of 1-carboxysalsolinol were found to be significantly greater in brains from alcoholics, who at autopsy had ethanol present in the blood, whereas alcoholics without blood ethanol levels at autopsy had significantly lower concentrations of salsolinol [27].
• The effects of two tetrahydroisoquinolines (TIQs), tetrahydropapaveroline (THP) and salsolinol (SAL), on human primary melanocytes were studied [28].
• According to enzymatic hydrolysis, 68% of 1-carboxysalsolinol was found as conjugates in urine, and the corresponding figure for salsolinol was 92% [27].

Gene context of C09642

• 1-Methyl-TIQ inhibited more potently MAO-A than MAO-B; the similar but more modest effect was exerted by salsolinol [29].
• These results suggest that salsolinol can play a pivotal role in the regulation of prolactin release induced by either physiological (suckling) or environmental (stress) stimuli [30].
• Our results show a significant decrease in the POMC gene expression by the S(-)-enantiomer of SAL [31].
• Taken together, these findings suggest that the reduction in cell surface TRPC1 protein expression in response to salsolinol may be a contributory factor in cellular toxicity of the dopaminergic neurons [20].
• Furthermore, MT overexpression may protect dopaminergic neurons against salsolinol-induced neurotoxicity, most probably by the inhibition of oxidative stress and apoptotic pathways including caspase-3 activation [21].

Analytical, diagnostic and therapeutic context of C09642

• N-Methylsalsolinol was detected in the brain dialysate samples during microdialysis with salsolinol using gas chromatography-mass spectrometry with selected-ion monitoring [32].
• Salsolinol determined by gas chromatography mass spectrometry was found to be present in the hypothalamus and the striatum of control rats [33].
• Confocal microscopy also showed that SH-SY5Y cells treated with salsolinol had a significant decrease in the plasma membrane staining of the TRPC1 protein [20].
• Immobilization stress-induced increase in plasma catecholamine levels is inhibited by a prolactoliberin (salsolinol) administration [34].
• On the fifth of a series of 5.0 min perfusions, either THP or salsolinol was added to the perfusion medium in a concentration of 10 or 100 ng/microliters [35].

References