NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys.
Prodrugs may be used to improve the absorption and bioavailability of certain active compounds. We have examined the ability of a novel catechol monoester of L-DOPA, NB-355 [L-3-(3-hydroxy-4-pivaloxyloyphenyl)alanine], to stimulate locomotor activity and induce dyskinesias in MPTP-treated primates....
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1989
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| _version_ | 1826262922824777728 |
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| author | Tye, S Rupniak, N Naruse, T Miyaji, M Iversen, S |
| author_facet | Tye, S Rupniak, N Naruse, T Miyaji, M Iversen, S |
| author_sort | Tye, S |
| collection | OXFORD |
| description | Prodrugs may be used to improve the absorption and bioavailability of certain active compounds. We have examined the ability of a novel catechol monoester of L-DOPA, NB-355 [L-3-(3-hydroxy-4-pivaloxyloyphenyl)alanine], to stimulate locomotor activity and induce dyskinesias in MPTP-treated primates. In the presence of carbidopa, a dose-dependent increase in locomotor activity over 4 1/2 h was observed following administration of L-DOPA (10, 20 or 40 mg/kg p.o.) or NB-355 (20, 40 or 80 mg/kg p.o. dopa equivalent). The dose-response curve for NB-355 was shifted to the right such that approximately twice the dopa equivalent dose of NB-355 was required to stimulate locomotor activity to the same level observed for L-DOPA. At doses matched for total locomotor stimulation over the 4 1/2-h period (20 mg/kg L-DOPA and 40 mg/kg NB-355), there was a more gradual rise and increase in the duration of motor stimulation by approximately 40% using NB-355. At these doses, drug-induced dyskinesias were less severe following treatment with NB-355 than with L-DOPA. Our findings suggest that NB-355 may be a useful therapeutic agent for increasing the duration of action of L-DOPA and reducing the severity of peak-dose dyskinesia. |
| first_indexed | 2024-03-06T19:43:30Z |
| format | Journal article |
| id | oxford-uuid:2177a37f-8a6a-4016-a876-0088ea9fa9d4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:43:30Z |
| publishDate | 1989 |
| record_format | dspace |
| spelling | oxford-uuid:2177a37f-8a6a-4016-a876-0088ea9fa9d42022-03-26T11:33:37ZNB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2177a37f-8a6a-4016-a876-0088ea9fa9d4EnglishSymplectic Elements at Oxford1989Tye, SRupniak, NNaruse, TMiyaji, MIversen, SProdrugs may be used to improve the absorption and bioavailability of certain active compounds. We have examined the ability of a novel catechol monoester of L-DOPA, NB-355 [L-3-(3-hydroxy-4-pivaloxyloyphenyl)alanine], to stimulate locomotor activity and induce dyskinesias in MPTP-treated primates. In the presence of carbidopa, a dose-dependent increase in locomotor activity over 4 1/2 h was observed following administration of L-DOPA (10, 20 or 40 mg/kg p.o.) or NB-355 (20, 40 or 80 mg/kg p.o. dopa equivalent). The dose-response curve for NB-355 was shifted to the right such that approximately twice the dopa equivalent dose of NB-355 was required to stimulate locomotor activity to the same level observed for L-DOPA. At doses matched for total locomotor stimulation over the 4 1/2-h period (20 mg/kg L-DOPA and 40 mg/kg NB-355), there was a more gradual rise and increase in the duration of motor stimulation by approximately 40% using NB-355. At these doses, drug-induced dyskinesias were less severe following treatment with NB-355 than with L-DOPA. Our findings suggest that NB-355 may be a useful therapeutic agent for increasing the duration of action of L-DOPA and reducing the severity of peak-dose dyskinesia. |
| spellingShingle | Tye, S Rupniak, N Naruse, T Miyaji, M Iversen, S NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys. |
| title | NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys. |
| title_full | NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys. |
| title_fullStr | NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys. |
| title_full_unstemmed | NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys. |
| title_short | NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys. |
| title_sort | nb 355 a novel prodrug for l dopa with reduced risk for peak dose dyskinesias in mptp treated squirrel monkeys |
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