I was more interested in the opening of the endocrine doorway. There are a huge number of studies that say melatonin is safe and helpful in PD. Against that you have a lone researcher, Dr. Willis, saying "Not so fast." The thing that gives me pause is that the reaction seems to have been to ignore him rather than to challenge his findings which involve the problem of an imbalance in the ratios of melatonin and dopamine. I don't know enough yet to take a position. But the man has a pretty good record of publications and he is not beating around the bush-

1: Physiol Behav. 1999 Jul;66(5):785-95.

A therapeutic role for melatonin antagonism in experimental models of
Parkinson's disease.

Willis GL, Armstrong SM.

The Bronowski Institute of Behavioural Neuroscience, Coliban Medical Centre,
Kyneton, Victoria, Australia.

To determine the effects of endogenous and exogenous melatonin on experimental
models of Parkinson's disease (PD), Sprague-Dawley rats were exposed to
intracerebroventricular implants of slow release melatonin, pinealectomy (PX),
or constant light (LL) and then injected with central 6-hydroxydopamine (6-OHDA)
or i.p. 1-methyl-4-phenyl,1-1,2,3,6-tetrahydropyridine (MPTP). The resulting
impairment of motor function and related behavioural impairment were exacerbated
by melatonin implantation, while PX and exposure to LL significantly reduced the
severity of experimental PD. These results are consistent with previous work
highlighting the importance of aberrant amine production in neurological disease
and demonstrate that treatments that reduce endogenous melatonin bioavailability
can ameliorate experimental PD. Furthermore, these findings illustrate that
melatonin is not the universal remedy that it is currently claimed to be, and
may pose considerable problems in neurological diseases characterised by
dopamine degeneration.

PMID: 10405106 [PubMed - indexed for MEDLINE]

and


1: Drug News Perspect. 2005 Sep;18(7):437-44.

The role of ML-23 and other melatonin analogues in the treatment and management
of Parkinson's disease.

Willis GL.

Bronowski Institute of Behavioural Neuroscience, Coliban Medical Centre,
Victoria, Australia. gwillbro@nex.net.au

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....


PMID: 16362083 [PubMed - indexed for MEDLINE]