The role of ML-23 and other melatonin analogues in the treatment and management of Parkinson's disease.
Contemporary theory regarding the cause and treatment of neuropsychiatric disease strongly suggests that as the human body ages it gradually loses the intrinsic safeguards that protect it from oxidative damage. Melatonin is one hormone that serves this function in that it possesses antioxidative properties in the mammalian body and brain. Melatonin has been shown to prevent the progressive degeneration produced by neurotoxins employed in experimental models to mimic the degenerative events in various neuropsychiatric disease states. There are an abundance of models for numerous disease states demonstrating that melatonin can inhibit oxidative stress and by such a mechanism it is presumed to exert a therapeutic effect. While a similar scenario has been revealed with in vitro work relating specifically to Parkinson's disease, clinical work with melatonin in this disorder demonstrates that it is devoid of any remarkable therapeutic effects. More recent preclinical and clinical work has reliably demonstrated that melatonin in fact may be without therapeutic efficacy and may even worsen the condition. On this pretense, attempts to reduce the bioavailability of melatonin using a melatonin receptor antagonist have been found to completely restore behavioral and regulatory function in the presence of chronically reduced levels of dopamine, without producing side effects commonly seen with traditional dopamine replacement therapy. The unavoidable conclusion from this work suggests that within the dynamic framework of the mammalian brain, hormones may play a duel, and possibly ambivalent, role in homeostasis and in the etiology of disease. Such a position requires a reevaluation of the etiology, the role of dopamine, the neurochemical characteristics of Parkinson's disease and the validity of the models employed to study this and other neuropsychiatric disorders.
Willis
Gregory L
GL
Bronowski Institute of Behavioural Neuroscience, Coliban Medical Centre, Victoria, Australia. gwillbro@nex.net.au
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use*; D008550:Melatonin / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology
D000978:Antiparkinson Agents; C053008:ML 23; D008735:5-Methoxytryptamine; D007980:Levodopa; D008550:Melatonin