Monoamine-oxidase B inhibitors

Deprenyl. Deprenyl, a selective monoamine oxidase B inhibitor that enhances dopaminergic function, is used in the treatment of Parkinson s disease. An open-label study (Jankovic et al., 1994) suggested that deprenyl could be effective for the treatment of ADHD in children with TS. A placebo-controlled crossover study (Feigin et al., 1996) of 24 subjects with ADHD and a tic disorder found that deprenyl was safe and effective at doses ranging from 5 to 10 mg/day. Only one subject showed an increase in tics. Interpretation of these results, however, is hampered by the clear evidence of an order effect. Subjects who received active drug first showed a 37% improvement in ADHD... 

The involvement of dopaminergic neurotransmission in AD has led to the use of agonists such as bromocriptine, lisuride, and pergolide, with poor results. A selective monoamine oxidase B inhibitor (MAO-B) such as deprenyl has also been employed. Little solid information exists on the effects of deprenyl on AD. Unfortunately, all information available comes from small studies. In a double-blind study, Tariot et al. (1987) observed that, with a daily dose of 10 mg in 17 patients with AD, a significant reduction in the scores for anxiety, depression, tension, and excitement was achieved. Burke et al. (1993), in a study of more than 20 patients with AD during a period of 15 months, found no behavioral changes in the progression of the illness nor in its scores. 

Tabakman R, Lecht S, Lazarovici P. Neuroprotection by monoamine oxidase B inhibitors a therapeutic strategy for Parkinson s disease Bioessays. 2004 26 80-90. 

L-deprenyl (selegiline), a monoamine oxidase B inhibitor, clonidine and guanfacine, a2-adreno-receptor agonists, and levodopa (L-dopa) have been reported to improve cognitive function in some subjects. Zimeldine, citaloprani, and alaproclate — selective serotonin uptake blockers — have no beneficial effects. 

Rasagiline, another monoamine oxidase B inhibitor, is more potent than selegiline in preventing MPTP-induced parkinsonism and is currently under study as a neuroprotective agent. 

Endo, Y., Hayashi, H., Sato, T., Maruno, M., Ohta, T., and Nozoe, S., 1994. Confluentic acid and 2 -0-methylperlatolic acid, monoamine oxidase B inhibitors in a Brazilian plant, Himatanthus sucuuba. Chem. Pharm. Bull. 42, 1198-1201. 

Monoamine-oxidase B inhibitors, such as selegiline and rasagiline, have a use alone in the management of early disease. Early treatment with selegiline alone has been shown to delay the need for levodopa therapy for some months, but other more effective drugs are preferred. Both dmgs can be used in conjunction with levodopa preparations to reduce end-of-dose deterioration in advanced disease. 

In the above described carbonylation reactions the nucleophile that reacts with the species released from the catalytic cycle is water or possibly an alcohol. This can be replaced by a more nucleophilic amine, yielding an amide as the product [66]. With this minor variation a different group of products becomes accessible. A striking application of this reaction is the synthesis of the monoamine oxidase B inhibitor Lazabemide [70, 75]. The first laboratory synthesis could be shortened from 8 steps to just one catalytic reaction with a TON of 3000 (Scheme 5.41). The only drawback to the greenness of this reaction is that the metal is removed via an extraction with aqueous NaCN. 

Use of monoamine oxidase B inhibitors (MAOB) to lengthen the duration of action of dopamine, by inhibiting its metabolism. 

Cytokines, such as tumor necrosis alfa and oxygen radicals, may be produced by HIV-infected macrophages or microglia. These substances cause apoptosis in the cerebral cortex and basal ganglia. Selegiline, also called deprenyl, and thioctic acid are monoamine oxidase-B inhibitors that have antioxidative effects and have been evaluated in tv o clinical hdals. Deprenyl has been previously studied in patients with Alzheimer s dementia and Parkinson s disease, showing improvement of memory in these conditions. 

Hence, it is not surprising that this type of carbonylation reaction has found application in industry. The pilot plant production of Lazabemide, a monoamine oxidase B inhibitor, by Hofmann-La Roche started from simple 2,5-dichloropyridine. The original eight-step laboratory synthesis of Lazabemide was replaced by a one-step protocol (eq. (11)) [56]. The product is isolated in 65 % yield. As only small amounts of catalyst have to be used (TON = 30(X)), traces of palladium in the product could be removed by appropriate work-up. 

Category Antidepressant Monoamine oxidase B inhibitor Half-life 9 minutes... 

Elsworth JD, Glover V, Reynolds GP, Sandler M, Lees AJ, Phuapradit P, Shaw KM, Stern GM, Kumar P (1978) Deprenyl administration in man a selective monoamine oxidase B inhibitor without the cheese effect . Psychopharmacology 57 33-38... 

Mann JJ, Gershon S (1980) A selective monoamine oxidase-B inhibitor in endogenous depression. life Sci 26 877-882 Mantle TJ, Garrett NJ, Tipton KF (1976) The development of monoamine oxidase in rat liver and brain. FEBS Lett 64 227-230... 

Monoamine oxidase-B inhibitors Selegiline Reduces metabolism of dopamine... 

Selegiline - monoamine oxidase-B inhibitor Parkinson s disease... 

The dopamine prodrug levodopa remains the treatment option for PD, however, long-term levodopa therapy leads to dyskinesia. Alternatives for early PD therapy include monoamine oxidase B inhibitors, dopamine agonists, catechol-O-methyltransferase (COMT) inhibitors, and amantadine (Hauser and Zesiewicz,... 

L-Deprenyl (Selegiline ), a selective monoamine oxidase-B inhibitor, in the treatment of early Parkinson s disease... 

Drug therapy is based on the severity of the disease. In the early phases of the disease, a monoamine oxidase B-inhibitor is used that inhibits dopamine degradation and decreases hydrogen peroxide formation. In later stages of the disease, patients are treated with levodopa (L-dopa), a precursor of dopamine. 

Macieod AD, Counseii CE, ives N, et ai. Monoamine oxidase B inhibitors for eariy Parkinson s disease. Cochrane Database Syst Rev 2005 3 CD004898, www.cochrane.org/reviews/en/ab004898.htmi. Accessed Aprii 2007. 

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