Rasagiline

Chemical compound

Rasagiline (Azilect, Azipron) is an irreversible inhibitor of monoamine oxidase B used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases. 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 Europe and Eisai in the US and elsewhere. It was approved in Europe in 2005 and in the US in 2006. Rasagiline is used to treat symptoms of Parkinson's disease both alone and in combination with other drugs. It has shown efficacy in both early and advanced Parkinsons, and appears to be especially useful in dealing with non motor symptoms like fatigue. Rasagiline has not been tested in pregnant women and is Pregnancy Category C in the US. Rasagiline prevents the breakdown of dopamine by irreversibly binding to MAO B. Dopamine is therefore more available, somewhat compensating for the diminished quantities made in the brains of people with Parkinson's. While these metabolites may contribute to selegiline's ability to inhibit reuptake of the neurotransmitters dopamine and norepinephrine, they have also been associated with orthostatic hypotension and hallucinations in some people. Rasagiline metabolizes into 1(R) aminoindan which has no amphetamine like characteristics and has neuroprotective properties in cells and in animal models.

Rasagiline is broken down via CYP1A2, part of the cytochrome P450 metabolic path in the liver. It is contraindicated in patients with hepatic insufficiency and its use should be monitored carefully in patients taking other drugs that alter the normal effectiveness of this metabolic path. At first, the N methyl was necessary for the agent to be considered a ring cyclized analog of pargyline with ca. twenty times the potency. However, the N methyl compound was a non selective MAOI. Racemic rasagiline was discovered and patented by Aspro Nicholas in the 1970s as a drug candidate for treatment of hypertension. Moussa B. H. Youdim, a biochemist, had been involved in developing selegiline as a drug for Parkinsons, in collaboration with Peter Reiderer. He wanted to find a similar compound that would have fewer side effects, and around 1977, at about the same time he moved from London to Haifa to join the faculty of Technion, he noticed that rasagiline could potentially be such a compound. He called that compound, AGN 1135. They called the mesylate salt of the R isomer TVP 1012 and the hydrochloride salt, TVP 101. 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 US in 2006.

Rasagiline was tested for efficacy in people with multiple system atrophy in a large randomized, placebo controlled, double blind disease modification trial; the drug failed.