TABLE 1.
Effects of melatonin in animal models of PD.
| References | Parkinsonism experimental model | Melatonin (dose and administration route | Effects of melatonin | Melatonin equivalent dose for a 75 kg adult patient a |
|---|---|---|---|---|
| Burton et al. (1991) | 6-OHDA SNc injections (Wistar rats) | 1 and 10 mg/ kg, i.p | Reduced apomorphine-induced rotational behavior | 12 and 120 mg |
| Acuña-Castroviejo et al. (1996) | MPP+ injection (C57BL/6 mice) | 10 mg/ kg, i.p | Reduced lipid peroxidation and TH-positive neuronal loss in striatum after MPP+ | 60 mg |
| Jin et al. (1998) | MPP+ SNc injection (Sprague-Dawley rats) | 10 mg/ kg, i.p | Reduced lipid peroxidation and protected against DA neuronal loss induced by MPP+ | 120 mg |
| Joo et al. (1998) | 6-OHDA striatal injections (Sprague-Dawley rats) | 3 and 10 mg/ kg, i.p | Increased striatal DA synthesis and levels | 36 and 120 mg |
| Kim et al. (1998) | 6-OHDA striatal injections (Sprague-Dawley rats) | 3 or 10 mg/ kg, i.p | Reduced motor deficit and improved dopaminergic neurons survival | 36 and 120 mg |
| DABBENI-SALA et al. (2001) | 6-OHDA nigral injections (Sprague-Dawley rats) | 50 ± 7.5 μg/ h, s.c | Prevented apomorphine-induced rotational behavior and mitochondrial damage | 15 mg |
| Aguiar et al. (2002) | 6-OHDA SNc injections (Wistar rats) | 2, 5, 10, and 25 mg/ kg, i.p | Prevented apomorphine-induced rotational behavior and depletion of striatal DA and serotonin levels | 24–300 mg |
| Chen et al. (2002) | MPP+ SNc injections (Wistar rats) | 10 mg/ kg, i.p.) | Decreased MPP+-induced toxicity and recovered GSH levels | 120 mg |
| Khaldy et al. (2003) | MPP+ injection (C57BL/6 mice) | 5 or 10 mg/ kg i.p | Increase in mitochondrial complex I activity in nigrostriatal neurons | 30 and 60 mg |
| Sharma et al. (2006) | 6-OHDA striatal injections (Sprague-Dawley rats) | 4 μg/ ml, p.o | Normalized motor deficits and augmented TH immunoreactivity | 6 mg |
| Singh et al. (2006) | 6-OHDA striatal injections (Sprague-Dawley rats) | 0.5 mg/ kg, i.p | Prevented apomorphine-induced rotational behavior | 6 mg |
| Saravanan et al. (2007) | Rotenone nigral injection (Sprague-Dawley rats) | 10, 20, or 30 mg/ kg, i.p | Reduced levels of hydroxyl radicals in mitochondria and increased GSH levels and antioxidant enzymes activities in SNc | 120, 240 and 360 mg |
| Huang et al. (2009) | MPP+ SNc injections (Wistar rats) | 10 mg/ kg, i.p | Reduced DA neurons apoptosis | 120 mg |
| Tapias et al. (2009) | MPTP injection (C57BL/6 mice) | 20 mg/ kg, s.c | Reduced mitochondrial NO levels, reduced lipid peroxidation and improved complex I activity in striatum and SNc | 120 mg |
| Patki and Lau, (2011) | MPTP injections for 5 weeks (C57BL/6 mice) | 5 mg/ kg, i.p | Reduced DA neurons loss and locomotor activity deficits. Improved mitochondrial respiration, ATP production, and antioxidant enzyme levels in SNc | 30 mg |
| Singhal et al. (2011) | Maneb plus paraquat (swiss mice) | 30 mg/ kg/day, i.p | Reduced lipid peroxidation, TH-positive neurons death, and apoptosis | 180 mg |
| Gutierrez-Valdez et al. (2012) | 6-OHDA media forebrain bundle injections (Wistar rats) | 10 mg/ kg, p.o | Improved motor performance without causing dyskinesia. Improved DA neurons survival | 120 mg |
| Brito-Armas et al. (2013) | Lentiviral vectors encoding mutant human a-synuclein injections in the SNc (Sprague-Dawley) | 10 mg/ kg/day, i.p | Improved DA neurons survival | 120 mg |
| Zaitone et al. (2013) | MPTP injections (swiss mice) | 5 or 10 mg/ kg/day, p.o | Improved motor performance, striatal DA level, GSH, and antioxidant enzyme activities, and reduced lipid peroxidation. Improved motor response to l-DOPA | 30 and 60 mg |
| Bassani et al. (2014) | Wistar rats were i.p. injected with rotenone | 10 mg/kg, i.p | Improved DA neurons survival and increased DA levels | 120 mg |
| Yildirim et al. (2014) | 6-OHDA injections into the medial forebrain bundle (Wistar rats) | 10 mg/ kg, i.p | Reduced oxidative damage and apoptosis of DA neurons | 120 mg |
| Naskar et al. (2015) | MPTP treatment in BALB/c mice | 10, 20 or 30 mg/ kg, i.p | Improved DA neurons survival and enhanced the therapeutic effect of l-DOPA | 60, 120 and 180 mg |
| Ozsoy et al. (2015) | 6-OHDA injections into the medial forebrain bundle (Wistar rats) | 10 mg/ kg/day, i.p | Improved DA neurons against antioxidant enzyme activities and reduced lipid peroxidation | 120 mg |
| Carriere et al. (2016) | Rotenone injections (Sprague Dawley rats) | 4.0 μg/ ml, p.o | Reduced motor deficit and DA neurons loss | 6 mg |
| Li et al. (2017) | 6-OHDA nigral injections (Wistar rats) | 5 mg/ kg, i.p | Reduced DA neuronal damage | 60 mg |
| López et al. (2017) | C57BL/6 mice receiving MPTP | 10 mg/ kg s.c | Preserved mitochondrial oxygen consumption, increased NOS activity and reduced locomotor activity | 60 mg |
| Paul et al. (2018) | Homocysteine SNc injections (Wistar rats) | 10, 20 or 30 mg/ kg/day, i.p | Reduced DA loss and improved mitochondrial complex-I activity in SN | 120, 240 and 360 mg |
| Rasheed et al. (2018) | Rotenone injections (Wistar rats) | 20 mg/ kg, i.p | Improved motor function by upregulation of tyrosine hydroxylase in striatum. Reduced DA neuron damage | 240 mg |
a
as calculated by normalization of body surface area (Reagan-Shaw et al., 2008) DA = dopamine; 6-OHDA = 6-hydroxydopamine; MPTP = 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPP+ = 1-methyl-4-phenylpyridinium; i.p. = intraperitoneal; s.c. = subcutaneous; p.o. = oral administration (in drinking water).