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. 1996

M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
Department of Biosciences, Nagoya Institute of Technology, Japan.

Dopamine-derived 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol, Sal) and related compounds were examined for their selective neurotoxicity to dopamine neurons by injection into the rat striatum. 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. Biochemical analysis showed that after NM(R)Sal injection, NM(R)Sal itself and its oxidation product, 1-2-dimethyl-6,7-dihydroxyisoquinolinium ion (DMDHIQ+) accumulated in the striatum, and also in the substantia nigra definite amount of DMDHIQ+ was detected. Dopamine and noradrenaline were reduced in the striatum and more markedly in the substantia nigra, whereas serotonin and its metabolite were not affected. Morphological analysis revealed selective reduction of tyrosine hydroxylase (TH)-containing neurons in the substantia nigra after continuous NM(R)Sal administration in the striatum. These results demonstrate the selective cytotoxicity of NM(R)Sal to the dopamine neurons in the substantia nigra, and the possible involvement of this 6,7-dihydroxy-isoquinoline in the pathogenesis of Parkinson's disease is discussed.

UI MeSH Term Description Entries
D007267 Injections Introduction of substances into the body using a needle and syringe. Injectables,Injectable,Injection
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D008297 Male Males
D010302 Parkinson Disease, Secondary Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42) Atherosclerotic Parkinsonism,Secondary Parkinsonism,Symptomatic Parkinson Disease,Parkinson Disease, Secondary Vascular,Parkinson Disease, Symptomatic,Parkinsonism, Secondary,Parkinsonism, Symptomatic,Secondary Vascular Parkinson Disease,Parkinsonism, Atherosclerotic,Secondary Parkinson Disease,Symptomatic Parkinsonism
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001522 Behavior, Animal The observable response an animal makes to any situation. Autotomy Animal,Animal Behavior,Animal Behaviors
D001679 Biogenic Amines A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. Amines, Biogenic,Biogenic Amine,Amine, Biogenic
D014446 Tyrosine 3-Monooxygenase An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2. Tyrosine Hydroxylase,3-Monooxygenase, Tyrosine,Hydroxylase, Tyrosine,Tyrosine 3 Monooxygenase

Related Publications

M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
June 1991, Biochemical and biophysical research communications,
M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
December 1995, European journal of pharmacology,
M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
January 1997, Chirality,
M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
July 2001, Brain research,
M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
June 2017, Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi,
M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
April 2012, Journal of neural transmission (Vienna, Austria : 1996),
M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
February 2000, Brain research,
M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
June 1969, Japanese journal of pharmacology,
M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
June 1964, Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft,
M Naoi, and W Maruyama, and P Dostert, and Y Hashizume, and D Nakahara, and T Takahashi, and M Ota
January 1993, Archives of toxicology,
Copied contents to your clipboard!