Azilect, a medication intended for Parkinson’s disease patients, developed and marketed by Teva Pharmaceuticals, according to research by Professor Moussa Youdim from the Faculty of Medicine, was approved for use in Europe and Israel in February 2005.
AGN-1135, the racemic form of the drug, was invented by Aspro Nicholas in the early 1970s. Moussa B. H. Youdim identified it as a potential drug for Parkinson’s disease, and working with collaborators at Technion – Israel Institute of Technology in Israel and the drug company, Teva Pharmaceuticals, identified the R-isomer as the active form of the drug.
Teva brought it to market in partnership with Lundbeck in the European Union and Eisai in the United States and elsewhere.
Prior to the discovery of rasagiline, a closely related analogue called SU-11739 (AGN-1133; J-508; N-methyl-N-propargyl-1-aminoindan) was patented in 1965.
At first, the N-methyl was necessary for the agent to be considered a ring cyclized analogue of pargyline with about 20 times the potency.
However, the N-methyl compound was a non-selective MAOI. In addition, SU-11739 has been reported to have strong catecholamine-releasing actions.
Racemic rasagiline was discovered and patented by Aspro Nicholas in the 1970s as a drug candidate for treatment of hypertension.
Moussa B. H. Youdim was involved in developing selegiline as a drug for Parkinson’s, in collaboration with Peter Reiderer.
He called the compound AGN 1135.
In 1996 Youdim, in collaboration with scientists from Technion and the US National Institutes of Health, and using compounds developed with Teva Pharmaceuticals, published a paper in which the authors wrote that they were inspired by the racemic nature of deprenyl and the greater activity of one of its stereoisomers, L-deprenyl, which became selegiline, to explore the qualities of the isomers of the Aspro compound, and they found that the R-isomer had almost all the activity; this is the compound that became rasagiline.
They called the mesylate salt of the R-isomer TVP-1012 and the hydrochloride salt, TVP-101.
Teva and Technion filed patent applications for this racemically pure compound, methods to make it, and methods to use it to treat Parkinson’s disease and other disorders, and Technion eventually assigned its rights to Teva.
Teva began development of rasagiline, and by 1999 was in Phase III trials, and entered into a partnership with Lundbeck in which Lundbeck agreed to share the costs and obtained the joint right to market the drug in the European Union.
In 2003, Teva partnered with Eisai, giving Eisai the right to jointly market the drug for Parkinson’s in the US, and to co-develop and co-market the drug for Alzheimers and other neurological diseases.
It was approved by the European Medicines Agency for Parkinson’s in 2005 and in the United States in 2006.
Following its approval, rasagiline was described by some authors as a “me-too drug” that offered nothing new in terms of effectiveness and tolerability compared to selegiline.
However, others have contended that rasagiline shows significant differences from and improvements over selegiline, like its lack of amphetamine metabolites and associated monoamine releasing agent effects, which may improve tolerability and safety.
Conversely, others have maintained that rasagiline may be less efficacious than selegiline due to its lack of catecholaminergic activity enhancer actions.