Apomorphine protects against MPTP-induced neurotoxicity in mice

• Published in: Movement disorders 1999-07, Vol.14 (4), p.612-618
• Main Authors: Grünblatt, Edna, Mandel, Silvia, Berkuzki, Tamara, Youdim, M. B. H.
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 6-tetrahydropyridine; Analysis of Variance; Animals; Antiparkinson Agents - pharmacology; Apomorphine; Apomorphine - pharmacology; Biological and medical sciences; Catecholaminergic system; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Disease Models, Animal; Dopamine; Dopamine - metabolism; Dopamine Agents; Iron; Male; Medical sciences; Mice; Mice, Inbred C57BL; Monoamine Oxidase - drug effects; Monoamine Oxidase - metabolism; Monoamine oxidase A and B; Monoamine Oxidase Inhibitors - pharmacology; MPTP (N-methyl-4-phenyl-1; MPTP (N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine); Neuropharmacology; Neuroprotective Agents - pharmacology; Neurotransmitters. Neurotransmission. Receptors; Oxidative Stress - drug effects; Parkinson Disease - etiology; Parkinson Disease - prevention & control; Parkinson's disease; Pharmacology. Drug treatments; Radical scavenging; Tyrosine 3-Monooxygenase - drug effects; Tyrosine 3-Monooxygenase - metabolism; Tyrosine hydroxylase
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/1531-8257(199907)14:4<612::AID-MDS1010>3.0.CO;2-6

R‐apomorphine is a potent radical scavenger and iron chelator. The neuroprotective property of R‐apomorphine, a dopamine D1‐D2 receptor agonist, has been studied in the MPTP (N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) model of Parkinson's disease. Pretreatment with 5–10 mg/kg R‐apomorphine administered subcutaneously in C57BL mice protects against MPTP (24 mg/kg administered intraperitoneally) induced loss of nigrostriatal dopamine neurons as indicated by striatal dopamine content, tyrosine hydroxylase content, and tyrosine hydroxylase activity. In vitro, R‐apomorphine inhibited mice striatal MAO‐A and MAO‐B activities with IC50 values of 93 μM and 241 μM. It is suggested that the neuroprotective effect of R‐apomorphine against MPTP neurotoxicity derives from its radical scavenging and MAO inhibitory actions and not from its agonistic activity because the mechanism of MPTP dopaminergic neurotoxicity involves the generation of oxygen radical species‐induced oxidative stress.