Hector Warnes’ response 2 to Joseph Knoll’s response

Joseph Knoll: The Discovery of the Enhancer Regulation in the Mammalian Brain and the Development of the Synthetic Enhancer Substances


            I am grateful to Professor Knoll for his partial response to my question. He cited two Datatop Multicenter studies of early Parkinson disease which demonstrated that L-Deprenyl, Selegiline, a MAO-B inhibitor, delayed the need for Levo-Dopa therapy, retards the spread of the disease and the onset of disability, while the anti-oxidant tocopherol (vitamin E) and/or rasagiline had no effect.

            Parkinson’s Disease, a neurodegenerative disease, appears usually after the age of 60 and is attributed to a loss of dopaminergic neurons within the substantia nigra. It has been shown that most changes in Parkinson’s Disease can be also found in the aging population, such as genetic factors; increased oxidative and inflammatory damage; dysfunction of intracellular calcium metabolism; and in protein degradation and mitochondrial activity.  The term “brain cellular senescence” has been used. It appears that the most outstanding difference is in the gene expression of alpha-synuclein (Park 1) and the deposit of iron in the substantia nigra. The particular pigmentation of the substantia nigra is due to neuromelatin’s accumulation. Neuromelatin binds iron and chelates it. In the general population, about 1% of people over 60 suffer from Parkinson’s Disease while more than 5% of them over 80 develop it.  An excellent review of the relationship between ageing and Parkinson’s Disease was published in 2014 by A. Reeve, E. Simcox and D. Turnbull.

            As a clinical psychiatrist, I do welcome new antidepressants and, from experience, have tested L-Deprenyl in Transdermal patches, which has been shown to be effective in a group of depressive patients.  We have not as yet identified the specificity of the various antidepressants with different locus of activity in the brain circuits and still we have to deal with a great number of chronic depressives who are refractory to several antidepressants, even to a combination of them. (I am sure Professor Knoll would sort out the characteristics of the group of patients who are responsive to MAO-B inhibitors.) It was also found that L-Deprenyl has neuroprotective action and improves cognitive functions, but so far it has not been clearly shown that it increases life span. L-Deprenyl metabolizes dopamine and phenylethylamine which are considered enhancer substances. As a clinician, I would worry about the side effects in the elderly population, particularly induced by drug interactions. It should not be given with narcotics, with oral oestrogens, with SSRIs inhibitors and so on.




Reeve A, Simcox E, Turnbull D.  Ageing and Parkinson’s disease: why is advancing age the biggest risk factor?  Ageing Research Reviews 2014; 14: 19-30.


January 4, 2018