Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies
The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity stimulated intense interest in neurotoxicology and in the possible toxic etiology of Parkinson's disease. Better understanding of MPTP neurotoxicity may be achieved by studies using 18F-radiolabeled MPTP analogs and p...
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1993
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| Online Access: | http://hdl.handle.net/10725/10440 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://jpet.aspetjournals.org/content/266/2/790.short |
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| author | Riachi, N.J. |
| author2 | Harik, S.I. Hritz, M.A. Berridge, M.S. Sayre, L.M. |
| author2_role | author author author author |
| author_facet | Riachi, N.J. Harik, S.I. Hritz, M.A. Berridge, M.S. Sayre, L.M. |
| author_role | author |
| dc.creator.none.fl_str_mv | Riachi, N.J. Harik, S.I. Hritz, M.A. Berridge, M.S. Sayre, L.M. |
| dc.date.none.fl_str_mv | 1993 2019-04-15T12:40:31Z 2019-04-15T12:40:31Z 2019-04-15 |
| dc.identifier.none.fl_str_mv | 0022-3565 http://hdl.handle.net/10725/10440 Harik, S. I., Riachi, N. J., Hritz, M. A., Berridge, M. S., & Sayre, L. M. (1993). Development of fluorinated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies. Journal of Pharmacology and Experimental Therapeutics, 266(2), 790-795. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://jpet.aspetjournals.org/content/266/2/790.short |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Journal of Pharmacology and Experimental Therapeutics |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity stimulated intense interest in neurotoxicology and in the possible toxic etiology of Parkinson's disease. Better understanding of MPTP neurotoxicity may be achieved by studies using 18F-radiolabeled MPTP analogs and positron emission tomography in nonhuman primates. We synthesized three fluorinated analogs of MPTP: 1-methyl-4-(2-fluorophenyl)-1,2,3,6-tetrahydropyridine (2'-F-MPTP), 1-methyl-4-[2-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine (2'-CF3-MPTP) and 1-methyl-4-[2-(fluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine (2'-CH2F-MPTP), and developed a method for preparing the latter in 18F-labeled form. We now studied the suitability of 2'-CH2F-MPTP and its hydrolysis products as substrates for monoamine oxidase (MAO) from mouse and monkey brain preparations, and investigated the neurotoxic effect of 2'-CH2F-MPTP and 2'-F-MPTP on the nigrostriatal dopaminergic system in mice. We found that 2'-CH2F-MPTP is a better substrate for MAO and that both 2'-CH2F-MPTP and 2'-F-MPTP were more potent neurotoxins than MPTP. Like MPTP, 2'-F-MPTP was exclusively oxidized by MAO-B and its toxicity blocked by pargyline or deprenyl but not by clorgyline. In contrast, 2'-CH2F-MPTP was oxidized by both MAO-A and MAO-B, and its toxicity was not blocked by pargyline, clorgyline or deprenyl when given separately, but required clorgyline and deprenyl together. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_5565fb107669a40bf2736f26cabd66b2 |
| identifier_str_mv | 0022-3565 Harik, S. I., Riachi, N. J., Hritz, M. A., Berridge, M. S., & Sayre, L. M. (1993). Development of fluorinated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies. Journal of Pharmacology and Experimental Therapeutics, 266(2), 790-795. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/10440 |
| publishDate | 1993 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studiesRiachi, N.J.Harik, S.I.Hritz, M.A.Berridge, M.S.Sayre, L.M.The discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity stimulated intense interest in neurotoxicology and in the possible toxic etiology of Parkinson's disease. Better understanding of MPTP neurotoxicity may be achieved by studies using 18F-radiolabeled MPTP analogs and positron emission tomography in nonhuman primates. We synthesized three fluorinated analogs of MPTP: 1-methyl-4-(2-fluorophenyl)-1,2,3,6-tetrahydropyridine (2'-F-MPTP), 1-methyl-4-[2-(trifluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine (2'-CF3-MPTP) and 1-methyl-4-[2-(fluoromethyl)phenyl]-1,2,3,6-tetrahydropyridine (2'-CH2F-MPTP), and developed a method for preparing the latter in 18F-labeled form. We now studied the suitability of 2'-CH2F-MPTP and its hydrolysis products as substrates for monoamine oxidase (MAO) from mouse and monkey brain preparations, and investigated the neurotoxic effect of 2'-CH2F-MPTP and 2'-F-MPTP on the nigrostriatal dopaminergic system in mice. We found that 2'-CH2F-MPTP is a better substrate for MAO and that both 2'-CH2F-MPTP and 2'-F-MPTP were more potent neurotoxins than MPTP. Like MPTP, 2'-F-MPTP was exclusively oxidized by MAO-B and its toxicity blocked by pargyline or deprenyl but not by clorgyline. In contrast, 2'-CH2F-MPTP was oxidized by both MAO-A and MAO-B, and its toxicity was not blocked by pargyline, clorgyline or deprenyl when given separately, but required clorgyline and deprenyl together.PublishedN/A2019-04-15T12:40:31Z2019-04-15T12:40:31Z19932019-04-15Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0022-3565http://hdl.handle.net/10725/10440Harik, S. I., Riachi, N. J., Hritz, M. A., Berridge, M. S., & Sayre, L. M. (1993). Development of fluorinated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies. Journal of Pharmacology and Experimental Therapeutics, 266(2), 790-795.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttp://jpet.aspetjournals.org/content/266/2/790.shortenJournal of Pharmacology and Experimental Therapeuticsinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/104402021-03-19T10:45:32Z |
| spellingShingle | Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies Riachi, N.J. |
| status_str | publishedVersion |
| title | Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies |
| title_full | Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies |
| title_fullStr | Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies |
| title_full_unstemmed | Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies |
| title_short | Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies |
| title_sort | Development of fluorinated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine analogs with potent nigrostriatal toxicity for potential use in positron emission tomography studies |
| url | http://hdl.handle.net/10725/10440 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php http://jpet.aspetjournals.org/content/266/2/790.short |