N-Methylnorsalsolinol
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| IUPAC name
2-methyl-3,4-dihydro-1H-isoquinoline-6,7-diol | |
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| ECHA InfoCard | 100.161.289 |
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| Properties | |
| C10H13NO2 | |
| Molar mass | 179.219 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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N-Methylnorsalsolinol (NMNSAL), also known as 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2-MDTIQ), is an endogenous dopaminergic neurotoxin, present in healthy individuals and at high levels in the cerebrospinal fluid of individuals with Parkinson's disease. Structurally, it is an isoquinolinol, which is norsalsolinol substituted with a methyl group at position 2. It can also be characterized as a rigid cyclized analogue of epinine.[1][2][3][4][5][6][7][8][9][10]
The biosynthesis of the neurotoxin N-methynorsalsolinol is carried out by enzymatic condensation of dopamine into salsolinol with its subsequent methylation under the action of neutral N-methyltransferase.[3] In rats and humans, the biosynthesis of the neurotoxin N-methylnorsalsolinol is carried out by Pictet-Spengler condensation from N-methyldopamine (epinine) and aldehydes.[4][5]
N-Methylnorsalsolinol has been detected as a metabolite in humans and rodents, as it is formed in the process of side metabolism of dopamine.[3]
Pharmacology
[edit]Pharmacodynamics
[edit]N-Methylnorsalsolinol has shown high biological activity. It inhibits the tyrosine hydroxylase enzyme in vitro.[7] It also inhibits the activity of the enzyme monoamine oxidase (In particular MAO-A), disrupting the natural breakdown of dopamine in the basal ganglia.[8][11] It probably also blocks the mechanisms of transport and uptake of neurotransmitters on the membranes of nerve cells.[12]
See also
[edit]References
[edit]- ↑ Moser, A.; Scholz, J.; Nobbe, F.; Vieregge, P.; Böhme, V.; Bamberg, H. (1995). "Presence of N-methyl-norsalsolinol in the CSF: correlations with dopamine metabolites of patients with Parkinson's disease". Journal of the Neurological Sciences. 131 (2): 183–189. doi:10.1016/0022-510x(95)00110-n. ISSN 0022-510X. PMID 7595645.
- ↑ Zhang, Wen; Xie, Yunfeng; Gu, Jing; Ai, Shiyun; Wang, Jian; Yamamoto, Katsunobu; Jin, Litong (2004). "Liquid chromatography with amperometric detection at a nano crystalline Ce-doped lead dioxide film modified electrode for determination of (R)-Salsolinol, (R)-N-methylsalsolinol and monoamine neurotransmitters in Parkinsonian patients' cerebrospinal fluid". The Analyst. 129 (3): 229–234. Bibcode:2004Ana...129..229Z. doi:10.1039/b314277a. ISSN 0003-2654. PMID 14978525.
- 1 2 3 Naoi, M.; Maruyama, W. (1999). "Cell death of dopamine neurons in aging and Parkinson's disease". Mechanisms of Ageing and Development. 111 (2–3): 175–188. doi:10.1016/s0047-6374(99)00064-0. ISSN 0047-6374. PMID 10656535.
- 1 2 Kajita, M.; Niwa, T.; Maruyama, W.; Nakahara, D.; Takeda, N.; Yoshizumi, H.; Tatematsu, A.; Watanabe, K.; Naoi, M.; Nagatsu, T. (1994-04-01). "Endogenous synthesis of N-methylnorsalsolinol in rat brain during in vivo microdialysis with epinine". Journal of Chromatography. B, Biomedical Applications. 654 (2): 263–269. doi:10.1016/0378-4347(94)00019-0. ISSN 1572-6495. PMID 8044287.
- 1 2 Kajita, M.; Niwa, T.; Takeda, N.; Yoshizumi, H.; Tatematsu, A.; Watanabe, K.; Nagatsu, T. (1993-03-05). "Presence of N-methyldopamine in parkinsonian and normal human brains". Journal of Chromatography. 613 (1): 1–8. doi:10.1016/0378-4347(93)80190-f. PMID 8458887.
- ↑ Thümen, Ansgar; Behnecke, Anne; Qadri, Fatimunnisa; Bäuml, Englbert; Thümen, Ansgar; Behnecke, C. Anne; Qadri, Fatimunnisa; Bäuml, Englbert; Moser, Andreas (2002-01-21). "N-methyl-norsalsolinol, a putative dopaminergic neurotoxin, passes through the blood-brain barrier in vivo". NeuroReport. 13 (1): 25–28. doi:10.1097/00001756-200201210-00010. ISSN 0959-4965. PMID 11924888.
- 1 2 Scholz, J.; Bamberg, H.; Moser, A. (1997). "N-methyl-norsalsolinol, an endogenous neurotoxin, inhibits tyrosine hydroxylase activity in the rat brain nucleus accumbens in vitro". Neurochemistry International. 31 (6): 845–849. doi:10.1016/s0197-0186(97)00028-4. ISSN 0197-0186. PMID 9413846.
- 1 2 Moser, A.; Scholz, J.; Bamberg, H.; Böhme, V. (1996). "The effect of N-methyl-norsalsolinol on monoamine oxidase of the rat caudate nucleus in vitro". Neurochemistry International. 28 (1): 109–112. doi:10.1016/0197-0186(95)00048-d. ISSN 0197-0186. PMID 8746770.
- ↑ Niwa, T.; Takeda, N.; Yoshizumi, H.; Tatematsu, A.; Yoshida, M.; Dostert, P.; Naoi, M.; Nagatsu, T. (1991-06-14). "Presence of 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline and 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, novel endogenous amines, in parkinsonian and normal human brains". Biochemical and Biophysical Research Communications. 177 (2): 603–609. Bibcode:1991BBRC..177..603N. doi:10.1016/0006-291x(91)91831-v. ISSN 0006-291X. PMID 2049084.
- ↑ Naoi, M.; Dostert, P.; Yoshida, M.; Nagatsu, T. (1993). "N-methylated tetrahydroisoquinolines as dopaminergic neurotoxins". Advances in Neurology. 60: 212–217. ISSN 0091-3952. PMID 8420137.
- ↑ Maruyama, W.; Nakahara, D.; Dostert, P.; Takahashi, A.; Naoi, M. (1993). "Naturally-occurring isoquinolines perturb monamine metabolism in the brain: studied by in vivo microdialysis". Journal of Neural Transmission. General Section. 94 (2): 91–102. doi:10.1007/BF01245003. PMID 7509158.
- ↑ Moser, A.; Siebecker, F.; Nobbe, F.; Böhme, V. (1996). "Rotational behaviour and neurochemical changes in unilateral N-methyl-norsalsolinol and 6-hydroxydopamine lesioned rats". Experimental Brain Research. 112 (1): 89–95. doi:10.1007/BF00227181. ISSN 0014-4819. PMID 8951410.