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.

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.