MAO-B is generally believed to break down  dopamine; however, recent evidence suggests that MAO-A may mostly or entirely be responsible for dopamine metabolism. 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 Parkinsons.Selegiline was the first selective MAO-B inhibitor. It is partly metabolized to levomethamphetamine (l-methamphetamine), one of the two enantiomers of methamphetamine, in vivo. While these metabolites may contribute to selegilines 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.It is selective for MAO type B over type A by a factor of fourteen. Metabolism
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. History
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.
Cobalt poisoning is intoxication caused by excessive levels of cobalt in the body. Cobalt is an essential element for health in animals in minute amounts as a component of Vitamin B12. A deficiency of cobalt, which is very rare, is also potentially lethal, leading to pernicious anemia.Exposure to cobalt metal dust is most common in the fabrication of tungsten carbide. Another source is from wear and tear of certain metal-on-metal hip prostheses.Per the International Agency for Research on Cancer (IARC), cobalt metal with tungsten carbide is "probably carcinogenic to humans" (IARC Group 2A Agent), whereas cobalt metal without tungsten carbide is "possibly carcinogenic to humans" (IARC Group 2B Agent). Cobalt salts
The LD50 value for soluble cobalt salts has been estimated to be between 150 and 500 mg/kg. Thus, for a 100 kg person the LD50 would be about 20 grams.Soluble cobalt(II) salts are "possibly carcinogenic to humans" (IARC Group 2B Agents). Beer drinkers cardiomyopathy
In August 1965, a person presented to a hospital in Quebec City with symptoms suggestive of alcoholic cardiomyopathy. Over the next eight months, fifty more cases with similar findings appeared in the same area with twenty of these being fatal. It was noted that all were heavy drinkers who mostly drank beer and preferred the Dow brand; thirty out of those drank more than 6 litres (12 pints) of beer per day.