Comparative Safety of Originator and Biosimilar Epoetin Alfa Drugs: An Observational Prospective Multicenter Study

Background: Erythropoiesis-stimulating agents (ESAs) are biological molecules approved for the treatment of anemia associated with chronic renal failure. Biosimilars were licensed for use in Europe in 2007. Aim: This study aimed to compare the safety profile of biosimilars with respect to the reference product in a nephrology setting. Methods: A prospective study was conducted in four Italian regions between 1 October 2013 and 30 June 2015. The study population included patients aged 65 18 years undergoing hemodialysis and treated with epoetins as per the clinical practice of the participating centers. The two comparison cohorts included patients treated with either an originator or a biosimilar epoetin alfa. Each patient was followed up until occurrence of any safety outcome of interest (grouped into three major categories), switch to a different ESA product, transplant or peritoneal dialysis, death, or end of the study period, whichever came first. Results: Overall, 867 subjects were included in the study (originator: N = 423; biosimilar: N = 444). Biosimilar users were older than originator users (median age of 76 vs 64 years, respectively), more frequently affected by arrhythmia (29.3 vs 22.5%), and less frequently candidates for transplantation (3.8 vs 18.2%). Cox-regression analysis showed no increase in risk of safety outcomes in biosimilar users, even after adjusting for confounding factors: 1.0 (95% confidence interval [CI] 0.7\u20131.3) for any outcomes; 1.1 (95% CI 0.7\u20131.8) for problems related to dialysis device; 0.9 (95% CI 0.6\u20131.5) for cardio- and cerebro-vascular conditions; 0.9 (95% CI 0.6\u20131.5) for infections. Conclusion: This study confirms the comparable safety profiles of originator and biosimilar epoetin alfa drugs when used in patients receiving dialysis

Focusing on new monoamine oxidase inhibitors

Importance of the field: Monoamine oxidase (MAO) plays a significant role in the control of intracellular concentration of monoaminergic neurotransmitters or neuromodulators and dietary amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critically important for the regulation of emotional and other brain functions. Furthermore, modulators of neurotransmitters exert pleiotropic effects on mental and cognitive functions. The by-products of MAO-mediated reactions include several chemical species with neurotoxic potential. It is widely speculated that prolonged or excessive activity of these enzymes may be conducive to mitochondrial damages and neurodegenerative disturbances. In keeping with these premises, the development of human MAO inhibitors has led to important breakthroughs in the therapy of several neuropsychiatric disorders. Areas covered in this review: This review highlights the recent MAO inhibitors related patents published from July 2005 to December 2009. It also reports on new associations of already known MAO inhibitors with other drugs, innovative therapeutic targets, MAO inhibitors obtained by plants extraction, alternative administration routes and synthetic processes. What the reader will gain: The reader will gain an overview of the main structures being investigated and their biological activities. Take home message: Several of these MAO inhibitors appear promising for further clinical development

The State of the Art of Pyrazole Derivatives as Monoamine Oxidase Inhibitors and Antidepressant/Anticonvulsant Agents

Monoamine oxidase plays a significant role in the control of intracellular concentration of monoaminergic neurotransmitters or neuromodulators and dietary amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critically important for the regulation of emotional and other brain functions. The development of human MAO inhibitors led to important breakthroughs in the therapy of several neuropsychiatric disorders. Different families of heterocycles containing 2 or 4 nitrogen atoms have been used as scaffolds for synthesizing selective monoamine oxidase inhibitors, but the early period of the MAO-inhibitors started with hydrazine derivatives. Pyrazole, pyrazoline, and pyrazolidine derivatives can be considered as a cyclic hydrazine moiety. This scaffold also displayed promising antidepressant and anticonvulsant properties as demonstrated by different and established animal models. Diversely substituted pyrazoles, embedded with a variety of functional groups, are important biological agents and a significant amount of research activity has been directed towards this chemical class

Patent-related survey on new monoamine oxidase inhibitors and their therapeutic potential

Introduction: Monoamine oxidase (MAO) plays an important role in the control of intracellular concentration of monoaminergic neurotransmitters or neuromodulators and dietary amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critical for the regulation of several mental and cognitive functions. The by-products of MAO-mediated reactions comprehend reactive and toxic chemical species. As a consequence of this, the development of human MAO inhibitors led to important discoveries in the treatment of several neuropsychiatric and neurodegenerative disorders. Areas covered: This review highlights the recent MAO inhibitors-related patents (2010-2012) and reports on new associations of already known MAO inhibitors with other drugs, innovative therapeutic targets, MAO inhibitors obtained by plants extraction, alternative administration routes and synthetic processes. Expert opinion: MAO inhibitors appear promising for further clinical development being often endowed with other pharmacological functions (iron-chelating property, cholinesterase inhibition). A new 'golden age' of MAO inhibitors recently started from (i) the discovery of new therapeutic targets (prostate cancer, diabetes, ischemia/reperfusion injury, tobacco dependence, transmissible spongiform encephalopathy); (ii) the recognized role of MAO as biomolecular markers (insomnia, chronic alcoholism, obsessive-compulsive behavior); (iii) the activity of these enzymes in other tissues (platelets, prostate cells)

A convenient procedure for the synthesis of diethynylbenzene derivatives.

A convenient 2-step synthesis of diethynylbenzenes is described, starting from the corresponding diacetyl derivs., via chlorination of the carbonyl functions with PCl5, followed by dehydrochlorination with Na/NH3(l)