Dopamine-derived endogenous 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl-(R)-salsolinol, induced parkinsonism in rat: biochemical, pathological and behavioral studies

Neuropathic alterations of the myenteric plexus neurons following subacute intraperitoneal administration of salsolinol

“…The distribution of the N-methylated and oxidized byproducts of salsolinol likely follow a certain pattern in the human nigrostriatal pathway and should therefore regulate the function of dopaminergic neurons [32]. Thus far, salsolinol and its metabolite N-methyl-salsolinol have been related to the neurodegeneration of central dopaminergic circuits and associated with the pathogenesis of Parkinson disease [19,20,[33][34][35]. We decided to investigate the salsolinol treatment as an experimental model in order to mimic gastrointestinal changes observed in patients with Parkinson's disease, in accordance with the Braak's hypothesis.…”

“…Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) might represent such a neurotoxic candidate. It can be easily endogenously synthesized from dopamine and acetaldehyde by salsolinol synthase or from dopamine and pyruvic acid or delivered exogenously [18][19][20].…”

Oxidative Stress and Neurodegenerative Disease

“…It is present in the human brain and can easily become a neurotoxin able to cause cell death. It has been proposed that this compound can be formed by an enzymatic pathway that involves a synthase or a nonenzymatic pathway by the condensation of the DA with acetaldehyde (Naoi et al, 1996).Another derivative of the DA is the tetrahydropapaveroline (THP), which is obtained from enzymatic catabolism. The THP by itself is able to cause necrosis in neuroblastom cells and is related to the pathogenesis of Parkinson's disease.…”

Effect of (R)-Salsolinol and N-Methyl-(R)-Salsolinol on the Balance Impairment Between Dopamine and Acetylcholine in Rat Brain: Involvement in Pathogenesis of Parkinson Disease

“…There is evidence supporting the hypothesis that (R)-Sal and (R)-NMSal may be involved in the etiology of PD. For example, (R)-Sal concentrations in the urine and cerebrospinal fluid from parkinsonian patients were significantly higher than those from controls (7,8 ), and (R)-NMSal has been shown to elicit a parkinsonian syndrome in rats (9 ). With recent advances in the understanding of PD, the crucial role of endogenous neurotoxins in the development of PD is increasingly apparent (10 ).…”