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Saturday, 25.03.2017

Comment (Ildikó Miklya)

In this book which Thomas Ban described in his Foreword as “the most impressive work, a tour de force, by one of the pioneers of neuropsychopharmacology” Joseph Knoll, the developer of (-)-deprenyl (D) (Selegiline) is summarizing from the early 1960s up to the present the development of his drug. At the beginning D became world-wide known as the first selective inhibitor of B-type monoamine oxidase (MAO), and was used in hundreds of laboratories as an important experimental tool in MAO research. D, described in thousands of papers, registered in 63 countries, and marketed under more than hundred trade names, is used to treat Parkinson’s disease (PD), Alzheimer’s disease (AD), and major depressive disorder (MDD). D is today the only available drug which as a specific β-phenylethylamine (PEA)-derived catecholaminergic activity enhancer (CAE) substance via a previously unknown mechanism, facilitates dopaminergic and trace-aminergic activity in the brain. From this monograph the reader will understand that PEA, a natural brain constituent is primarily a CAE substance. Because in higher dose range PEA is a strong releaser of catecholamines from their intra-neuronal pools, this effect concealed its physiological CAE effect, and this property remained undetected. Amphetamine and methamphetamine, the PEA derivatives with a long-lasting effect act like their parent compound. In low concentrations they are also CAE substances. The development of D, the only PEA-derivative which preserved its CAE effect but completely lost its catecholamine-releasing property, enabled the discovery of the enhancer regulation in the catecholaminergic and serotonergic neurons. In a chapter of this book the author clarifies how his finding that tryptamine is like PEA a natural enhancer of the catecholaminergic and serotonergic neurons inspired him to develop between 1995 and 1999 R-(-)-1-(benzofuran-2yl)-2-propylaminopentane [(-)-BPAP], a tryptamine-derived selective enhancer substance which exerts this effect in femto-picomolar concentrations. In the last chapter experimental evidence is presented for the importance of (-)-BPAP in the operation of enhancer regulation. Nevertheless, it seems to me that the main aim of the author with this book was to convince clinicians that time is ripe for a proper trial to test the anti-aging effect of preventive D treatment. Let me quote this message of the author with his own words: “It is the main aim of this book to piece facts and arguments together which all goes to show that selegiline, due to its CAE effect, slows the aging-related decay of the catecholaminergic brain engine, and this is why the maintenance on a low daily dose of selegiline helps to maintain physical and mental vigor in the latter decades of life, and is also a chance to significantly decrease the prevalence of PD and AD. To motivate clinicians to think the matter over inspired this work.”

Ildikó Miklya
October 17, 2013