Oral r-(-)-11-o-valeryl-n-n-propylnoraporphine reverses motor deficits in mptp-treated marmosets

Abstract

Oral administration of 11-OH-NPa valerate produced a rapid reversal of motor disability and, at effective dose levels, had a limited propensity to induce dyskinesia. 11-OH-NPa valerate is the first orally active derivative of apomorphine with potential for use in PD. © 2016 International Parkinson and Movement Disorder Society.

Neurotoxin-Induced Animal Models of Parkinson Disease: Pathogenic Mechanism and Assessment

“…Nonhuman primates treated with MPTP develop motor defects that closely resemble the behaviors in PD, including bradykinesia, rigidity and postural abnormalities, as well as other pathophysiological changes observed in PD patients, so the MPTP-treated monkey has been recognized as the gold standard model of PD ( Masilamoni and Smith, 2017 ). Common marmosets were subcutaneously administrated with MPTP (2.0 mg/kg) once daily for 5 days and exhibited significant and stable motor deficits, including a marked reduction in basal locomotor activity, poor coordination of movement, abnormal or rigid posture, reduced alertness, and head-checking movements ( Lincoln et al., 2016 ). The adult male cynomolgus monkeys, intravenously injected with MPTP (0.4 mg/kg) twice a week for more than 12 weeks, displayed stable parkinsonian symptoms, such as tremor, bradykinesia, and impaired balance ( Kikuchi et al., 2017 ).…”

Pharmacological Insights into Levodopa‐induced Motor Fluctuations in Patients with Parkinson's Disease

“…An orally active formulation would significantly broaden the spectrum of patients who could benefit from apomorphine. The article by Lincoln and colleagues in this Supplement suggests that such a formulation might be feasible in the future, as shown by their encouraging experimental results in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetra hydropyridine (MPTP)‐treated marmosets using a novel, orally active, apomorphine‐related compound: R‐(‐)‐11‐O‐valeryl‐N‐n‐propylnoraporphine.…”