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Selective monoamine oxidase type B MAOB inhibitors - Biotech, Pharma and Life Science Channel

08:56 EST 13th December 2018 | BioPortfolio

The clinical benefit of monoamine oxidase type B (MAO-B) inhibitors is thought to arise from an ability of these medications to enhance the level of dopamine by decreasing the catabolism. Additionally, basic research suggests that MAO-B inhibitors may impart efficacy by inhibiting apoptosis (programmed cell death). There are two MAO-B inhibitors available today, selegiline and rasagiline.

Selegiline is an irreversible, relatively selective (its selectivity is lost at higher doses) MAO-B inhibitor. Selegiline possesses other pharmacological activities such as an effect on mitochondrial membrane potential activity, an antiapoptosis effect and reduction of oxidative stress which may play a role in its putative neuroprotective effect. When administered orally, selegiline has low bioavailability as a result of extensive hepatic first-pass metabolism. This metabolism produces high levels of amphetamine metabolites; l-methamphetamine and l-amphetamine account for more than three-fourths of the recovered metabolites from an oral dose of conventional selegiline. There is also an orally disintegrating tablet (ODT) of selegiline which has advantages including rapid onset of action, avoidance of presystemic metabolism to provide higher drug levels and decreased plasma concentrations of amphetamine metabolites.

Azilect or Rasagiline and its analogues are under investigation for Alzheimer's disease. They apparently enhance memory and learning. Rasagiline may also improve mood, motivation and age-related memory decline in the ageing but nominally well adult population.

 The novel cholinesterase-brain selective MAO-AB inhibitor, TV3326, a carbamte derivative of the irreversible MAO-B inhibitor anti-Parkinson drug, rasagiline is a brain selective MAO-A and B inhibitor, with little inhibition of liver and small intestine enzymes. Pharmacologically it has limited tyramine potentiation, very similar to moclobemide and being a MAO-AB inhibitor it has the antidepressant, anti-Parkinson and anti-Alzheimer activities in the respective models used to develop such drugs.

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Medical and Biotech [MESH] Definitions

A reversible inhibitor of monoamine oxidase type A; (RIMA); (see MONOAMINE OXIDASE INHIBITORS) that has antidepressive properties.

An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4.

One of the MONOAMINE OXIDASE INHIBITORS used to treat DEPRESSION; PHOBIC DISORDERS; and PANIC.

An adverse drug interaction characterized by altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It is most frequently caused by use of both serotonin reuptake inhibitors and monoamine oxidase inhibitors, leading to excess serotonin availability in the CNS at the serotonin 1A receptor.

A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl.

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