A dual dopaminergic therapy with L-3,4-dihydroxyphenylalanine and chlorpromazine for the treatment of blepharospasm, a focal dystonia: Possible implications for striosomal D1 signaling
Impairment of balanced activity between dopamine D1 and D2 receptor functions in the striatum, particularly in striatal functional subdivisions (i.e., striosome and matrix compartments), has been proposed to underlie dystonia genesis. This study was undertaken to examine the therapeutic effect of du...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2022.922333/full |
| _version_ | 1818190013984145408 |
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| author | Shinichi Matsumoto Hidetaka Koizumi Hideki Shimazu Hideki Shimazu Ryuji Kaji Satoshi Goto Satoshi Goto |
| author_facet | Shinichi Matsumoto Hidetaka Koizumi Hideki Shimazu Hideki Shimazu Ryuji Kaji Satoshi Goto Satoshi Goto |
| author_sort | Shinichi Matsumoto |
| collection | DOAJ |
| description | Impairment of balanced activity between dopamine D1 and D2 receptor functions in the striatum, particularly in striatal functional subdivisions (i.e., striosome and matrix compartments), has been proposed to underlie dystonia genesis. This study was undertaken to examine the therapeutic effect of dual dopaminergic modulation with L-3,4-dihydroxyphenylalanine (L-DOPA) and chlorpromazine (CPZ) in patients with blepharospasm, a focal dystonia. For this purpose, Dopacol tablets™ (L-DOPA 50 mg plus carbidopa 5 mg) and Wintermin™ (CPZ phenolphthalinate 180 mg/g) were used. Clinical evaluations were performed before and after an 8-week drug treatment interval using the Visual Analog Scale (VAS), Blepharospasm Disability Index (BSDI), modified VAS (mVAS), and Jankovic Rating Scale (JRS). The data were analyzed using non-parametric statistics. Results showed that in patients (n = 7) with blepharospasm, dystonia symptoms were significantly alleviated by the administration of both Dopacol tablets™ (one tablet × 3/day) and CPZ (5 mg × 3/day), as determined using the VAS, BSDI, mVAS, and JRS. In contrast, there was no improvement of dystonia symptoms in patients (n = 7) who ingested Dopacol tablets™ (one tablet × 3/day) alone, nor in those (n = 7) who ingested CPZ (5 mg × 3/day) alone. Thus, dual pharmacotherapy with L-DOPA and CPZ can exert a therapeutic effect on blepharospasm, suggesting that dystonia symptoms can be attenuated through dopaminergic modulation with inducing an increase in striatal D1-signals. Since dopamine D1 receptors are heavily enriched in the striosome compartment in the “human” striatum, our results also suggest that striosomal loss of D1-signaling may be important in the pathogenesis of dystonia. |
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| id | doaj.art-25a2e10c22c54628b7d189f342697b8e |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-11T23:51:58Z |
| publishDate | 2022-07-01 |
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| spelling | doaj.art-25a2e10c22c54628b7d189f342697b8e2022-12-22T00:45:27ZengFrontiers Media S.A.Frontiers in Neurology1664-22952022-07-011310.3389/fneur.2022.922333922333A dual dopaminergic therapy with L-3,4-dihydroxyphenylalanine and chlorpromazine for the treatment of blepharospasm, a focal dystonia: Possible implications for striosomal D1 signalingShinichi Matsumoto0Hidetaka Koizumi1Hideki Shimazu2Hideki Shimazu3Ryuji Kaji4Satoshi Goto5Satoshi Goto6Department of Neurology, Osaka Neurological Institute, Toyonaka, JapanDepartment of Neurology, Kyoto Prefectural Rehabilitation Hospital for the Disabled, Nakaashihara, Kyoto, JapanDepartment of Neurology, Itsuki Hospital, Tokushima, JapanDepartment of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, JapanDepartment of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University, Tokushima, JapanDepartment of Clinical Neuroscience, Institute of Biomedical Sciences, Tokushima University, Tokushima, JapanCenter for Drug Discovery and Development Sciences, Research Organization of Science and Technology, Ritsumeikan University, Kyoto, JapanImpairment of balanced activity between dopamine D1 and D2 receptor functions in the striatum, particularly in striatal functional subdivisions (i.e., striosome and matrix compartments), has been proposed to underlie dystonia genesis. This study was undertaken to examine the therapeutic effect of dual dopaminergic modulation with L-3,4-dihydroxyphenylalanine (L-DOPA) and chlorpromazine (CPZ) in patients with blepharospasm, a focal dystonia. For this purpose, Dopacol tablets™ (L-DOPA 50 mg plus carbidopa 5 mg) and Wintermin™ (CPZ phenolphthalinate 180 mg/g) were used. Clinical evaluations were performed before and after an 8-week drug treatment interval using the Visual Analog Scale (VAS), Blepharospasm Disability Index (BSDI), modified VAS (mVAS), and Jankovic Rating Scale (JRS). The data were analyzed using non-parametric statistics. Results showed that in patients (n = 7) with blepharospasm, dystonia symptoms were significantly alleviated by the administration of both Dopacol tablets™ (one tablet × 3/day) and CPZ (5 mg × 3/day), as determined using the VAS, BSDI, mVAS, and JRS. In contrast, there was no improvement of dystonia symptoms in patients (n = 7) who ingested Dopacol tablets™ (one tablet × 3/day) alone, nor in those (n = 7) who ingested CPZ (5 mg × 3/day) alone. Thus, dual pharmacotherapy with L-DOPA and CPZ can exert a therapeutic effect on blepharospasm, suggesting that dystonia symptoms can be attenuated through dopaminergic modulation with inducing an increase in striatal D1-signals. Since dopamine D1 receptors are heavily enriched in the striosome compartment in the “human” striatum, our results also suggest that striosomal loss of D1-signaling may be important in the pathogenesis of dystonia.https://www.frontiersin.org/articles/10.3389/fneur.2022.922333/fullblepharospasmdystoniaL-DOPAchlorpromazinedopamine D1 receptorstriatum |
| spellingShingle | Shinichi Matsumoto Hidetaka Koizumi Hideki Shimazu Hideki Shimazu Ryuji Kaji Satoshi Goto Satoshi Goto A dual dopaminergic therapy with L-3,4-dihydroxyphenylalanine and chlorpromazine for the treatment of blepharospasm, a focal dystonia: Possible implications for striosomal D1 signaling Frontiers in Neurology blepharospasm dystonia L-DOPA chlorpromazine dopamine D1 receptor striatum |
| title | A dual dopaminergic therapy with L-3,4-dihydroxyphenylalanine and chlorpromazine for the treatment of blepharospasm, a focal dystonia: Possible implications for striosomal D1 signaling |
| title_full | A dual dopaminergic therapy with L-3,4-dihydroxyphenylalanine and chlorpromazine for the treatment of blepharospasm, a focal dystonia: Possible implications for striosomal D1 signaling |
| title_fullStr | A dual dopaminergic therapy with L-3,4-dihydroxyphenylalanine and chlorpromazine for the treatment of blepharospasm, a focal dystonia: Possible implications for striosomal D1 signaling |
| title_full_unstemmed | A dual dopaminergic therapy with L-3,4-dihydroxyphenylalanine and chlorpromazine for the treatment of blepharospasm, a focal dystonia: Possible implications for striosomal D1 signaling |
| title_short | A dual dopaminergic therapy with L-3,4-dihydroxyphenylalanine and chlorpromazine for the treatment of blepharospasm, a focal dystonia: Possible implications for striosomal D1 signaling |
| title_sort | dual dopaminergic therapy with l 3 4 dihydroxyphenylalanine and chlorpromazine for the treatment of blepharospasm a focal dystonia possible implications for striosomal d1 signaling |
| topic | blepharospasm dystonia L-DOPA chlorpromazine dopamine D1 receptor striatum |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2022.922333/full |
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