Antiallodynic Action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a Betaine/GABA Transporter Inhibitor
Abstract.: The GABAergic system in the spinal cord has been shown to participate in neuropathic pain in various animal models. GABA transporters (GATs) play a role in controlling the synaptic clearance of GABA; however, their role in neuropathic pain remains unclear. In the present study, we compare...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319301458 |
| _version_ | 1818027439678291968 |
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| author | Ayako Jinzenji Chiharu Sogawa Takuya Miyawaki Xue-fang Wen Dan Yi Kazumi Ohyama Shigeo Kitayama Norio Sogawa Katsuya Morita |
| author_facet | Ayako Jinzenji Chiharu Sogawa Takuya Miyawaki Xue-fang Wen Dan Yi Kazumi Ohyama Shigeo Kitayama Norio Sogawa Katsuya Morita |
| author_sort | Ayako Jinzenji |
| collection | DOAJ |
| description | Abstract.: The GABAergic system in the spinal cord has been shown to participate in neuropathic pain in various animal models. GABA transporters (GATs) play a role in controlling the synaptic clearance of GABA; however, their role in neuropathic pain remains unclear. In the present study, we compared the betaine/GABA transporter (BGT-1) with other GAT subtypes to determine its participation in neuropathic pain using a mouse model of sciatic nerve ligation. 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), an inhibitor that displays moderate selectivity for BGT-1, had an antiallodynic action on model mice treated through both intrathecally and intravenous administration routes. On the other hand, SKF89976A, a selective GAT-1 inhibitor, had a weak antiallodynic action, and (S)-SNAP5114, an inhibitor that displays selectivity for GAT-3, had no antiallodynic action. Systemic analysis of these compounds on GABA uptake in CHO cells stably expressing BGT-1 revealed that NNC05-2090 not only inhibited BGT-1, but also serotonin, noradrenaline, and dopamine transporters, using a substrate uptake assay in CHO cells stably expressing each transporter, with IC50: 5.29, 7.91, and 4.08 μM, respectively. These values were similar to the IC50 value at BGT-1 (10.6 μM). These results suggest that the antiallodynic action of NNC05-2090 is due to the inhibition of both BGT-1 and monoamine transporters. Keywords:: neuropathic pain, betaine/GABA transporter, monoamine transporter, NNC05-2090, antiallodynic action |
| first_indexed | 2024-12-10T04:47:55Z |
| format | Article |
| id | doaj.art-7a8ceb6c96eb48a485de19a2de948d9d |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T04:47:55Z |
| publishDate | 2014-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-7a8ceb6c96eb48a485de19a2de948d9d2022-12-22T02:01:42ZengElsevierJournal of Pharmacological Sciences1347-86132014-01-011252217226Antiallodynic Action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a Betaine/GABA Transporter InhibitorAyako Jinzenji0Chiharu Sogawa1Takuya Miyawaki2Xue-fang Wen3Dan Yi4Kazumi Ohyama5Shigeo Kitayama6Norio Sogawa7Katsuya Morita8Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan; Department of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, JapanDepartment of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, JapanDepartment of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, JapanDepartment of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, JapanDepartment of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, JapanRI Research Center, Okayama University Dental School, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, JapanDepartment of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, JapanDepartment of Dental Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan; Correspondence author. sogawa@md.okayama-u.ac.jpDepartment of Pharmacology, Faculty of Nursing, Hiroshima Bunka Gakuen University, 2-10-3 Agaminami, Kure-city, Hiroshima 737-0004, JapanAbstract.: The GABAergic system in the spinal cord has been shown to participate in neuropathic pain in various animal models. GABA transporters (GATs) play a role in controlling the synaptic clearance of GABA; however, their role in neuropathic pain remains unclear. In the present study, we compared the betaine/GABA transporter (BGT-1) with other GAT subtypes to determine its participation in neuropathic pain using a mouse model of sciatic nerve ligation. 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), an inhibitor that displays moderate selectivity for BGT-1, had an antiallodynic action on model mice treated through both intrathecally and intravenous administration routes. On the other hand, SKF89976A, a selective GAT-1 inhibitor, had a weak antiallodynic action, and (S)-SNAP5114, an inhibitor that displays selectivity for GAT-3, had no antiallodynic action. Systemic analysis of these compounds on GABA uptake in CHO cells stably expressing BGT-1 revealed that NNC05-2090 not only inhibited BGT-1, but also serotonin, noradrenaline, and dopamine transporters, using a substrate uptake assay in CHO cells stably expressing each transporter, with IC50: 5.29, 7.91, and 4.08 μM, respectively. These values were similar to the IC50 value at BGT-1 (10.6 μM). These results suggest that the antiallodynic action of NNC05-2090 is due to the inhibition of both BGT-1 and monoamine transporters. Keywords:: neuropathic pain, betaine/GABA transporter, monoamine transporter, NNC05-2090, antiallodynic actionhttp://www.sciencedirect.com/science/article/pii/S1347861319301458 |
| spellingShingle | Ayako Jinzenji Chiharu Sogawa Takuya Miyawaki Xue-fang Wen Dan Yi Kazumi Ohyama Shigeo Kitayama Norio Sogawa Katsuya Morita Antiallodynic Action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a Betaine/GABA Transporter Inhibitor Journal of Pharmacological Sciences |
| title | Antiallodynic Action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a Betaine/GABA Transporter Inhibitor |
| title_full | Antiallodynic Action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a Betaine/GABA Transporter Inhibitor |
| title_fullStr | Antiallodynic Action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a Betaine/GABA Transporter Inhibitor |
| title_full_unstemmed | Antiallodynic Action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a Betaine/GABA Transporter Inhibitor |
| title_short | Antiallodynic Action of 1-(3-(9H-Carbazol-9-yl)-1-propyl)-4-(2-methyoxyphenyl)-4-piperidinol (NNC05-2090), a Betaine/GABA Transporter Inhibitor |
| title_sort | antiallodynic action of 1 3 9h carbazol 9 yl 1 propyl 4 2 methyoxyphenyl 4 piperidinol nnc05 2090 a betaine gaba transporter inhibitor |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319301458 |
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