The nociceptin/orphanin FQ (NOP) receptor antagonist J-113397 enhances the effects of levodopa in the MPTP-lesioned nonhuman primate model of Parkinson's disease

Naomi P. Visanji; Rob M. A. de Bie; Tom H. Johnston; Andrew C. McCreary; Jonathan M. Brotchie; Susan H. Fox

doi:https://doi.org/10.1002/mds.22086

The nociceptin/orphanin FQ (NOP) receptor antagonist J-113397 enhances the effects of levodopa in the MPTP-lesioned nonhuman primate model of Parkinson's disease

Naomi P. Visanji, Rob M. A. de Bie, Tom H. Johnston, Andrew C. McCreary, Jonathan M. Brotchie, Susan H. Fox

Research output: Contribution to journal › Article › Academic › peer-review

34 Citations (Scopus)

Abstract

The anti-parkinsonian and levodopa-sparing potential of the nociceptin/orphanin FQ receptor (NOP) antagonist J-113397 has been demonstrated in rodent models of Parkinson's disease. Here, we describe the levodopa-sparing potential of J-113397 in MPTP-lesioned marmosets. Coadministration of J-113397 (30 mg/kg) with a sub-therapeutic dose of levodopa (12.5 mg/kg) produced an anti-parkinsonian action equivalent to that of a therapeutic dose of levodopa. However, these effects were accompanied by an equivalent level of dyskinesia. The actions of NOP antagonists seen in rodents translate to nonhuman primates. However, the present study raises the possibility that these levodopa-sparing benefits may be offset by a propensity to exacerbate dyskinesia

Original language	English
Pages (from-to)	1922-1925
Journal	Movement disorders
Volume	23
Issue number	13
DOIs	https://doi.org/10.1002/mds.22086
Publication status	Published - 2008

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https://doi.org/10.1002/mds.22086

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title = "The nociceptin/orphanin FQ (NOP) receptor antagonist J-113397 enhances the effects of levodopa in the MPTP-lesioned nonhuman primate model of Parkinson's disease",

abstract = "The anti-parkinsonian and levodopa-sparing potential of the nociceptin/orphanin FQ receptor (NOP) antagonist J-113397 has been demonstrated in rodent models of Parkinson's disease. Here, we describe the levodopa-sparing potential of J-113397 in MPTP-lesioned marmosets. Coadministration of J-113397 (30 mg/kg) with a sub-therapeutic dose of levodopa (12.5 mg/kg) produced an anti-parkinsonian action equivalent to that of a therapeutic dose of levodopa. However, these effects were accompanied by an equivalent level of dyskinesia. The actions of NOP antagonists seen in rodents translate to nonhuman primates. However, the present study raises the possibility that these levodopa-sparing benefits may be offset by a propensity to exacerbate dyskinesia",

author = "Visanji, {Naomi P.} and {de Bie}, {Rob M. A.} and Johnston, {Tom H.} and McCreary, {Andrew C.} and Brotchie, {Jonathan M.} and Fox, {Susan H.}",

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AU - Visanji, Naomi P.

AU - de Bie, Rob M. A.

AU - Johnston, Tom H.

AU - McCreary, Andrew C.

AU - Brotchie, Jonathan M.

AU - Fox, Susan H.

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AB - The anti-parkinsonian and levodopa-sparing potential of the nociceptin/orphanin FQ receptor (NOP) antagonist J-113397 has been demonstrated in rodent models of Parkinson's disease. Here, we describe the levodopa-sparing potential of J-113397 in MPTP-lesioned marmosets. Coadministration of J-113397 (30 mg/kg) with a sub-therapeutic dose of levodopa (12.5 mg/kg) produced an anti-parkinsonian action equivalent to that of a therapeutic dose of levodopa. However, these effects were accompanied by an equivalent level of dyskinesia. The actions of NOP antagonists seen in rodents translate to nonhuman primates. However, the present study raises the possibility that these levodopa-sparing benefits may be offset by a propensity to exacerbate dyskinesia

U2 - https://doi.org/10.1002/mds.22086

DO - https://doi.org/10.1002/mds.22086

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