Monoamine oxidase types

Future Outlook for Antidepressants. Third-generation antidepressants are expected to combine superior efficacy and improved safety, but are unlikely to reduce the onset of therapeutic action in depressed patients (179). Many dmgs in clinical development as antidepressive agents focus on estabhshed properties such as inhibition of serotonin, dopamine, and/or noradrenaline reuptake, agonistic or antagonistic action at various serotonin receptor subtypes, presynaptic tt2-adrenoceptor antagonism, or specific monoamine—oxidase type A inhibition. Examples include buspirone (3) (only... 

Da Prada, M, Kettler, R, Keller, HH, Burkard, WP, Muggli-Maniglio, D and Haefely, WE (1989) Neurochemical profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A. /. Pharmacol. Exp. Ther. 248 400-414. 

The beneficial effect of deprenyl in Parkinson s disease was su ested to be in part due to its effect on increasing the levels of SOD activity in several brain regions (Carrillo et al., 1993). Deprenyl is known to inhibit monoamine oxidase type B, which results in a reduction in hydrogen peroxide formation by blockade of the oxidative deamination of dopamine. That is believed to be the major mechanism of action of this drug in inhibiting the progression of Parkinson s disease. 

MAOa Monoamine oxidase type A NSAID non-steroidal anti-inflammatory drug SSRI selective serotonin reuptake inhibitors... 

Which of the following is a selective inhibitor of monoamine oxidase type B (MAO-B) and, therefore, useful in treating parkinsonism ... 

Monoamine oxidase type B activity is increased / Glutamate pathways of the cortex and limbic structures are abnormal... 

Fowler CJ, Mantle TJ, Tipton KF. The nature of the inhibition of rat liver monoamine oxidase types A and B by the acetylenic inhibitors clorgyline, 1-deprenyl and pargyline. Biochem Pharmacol 1982 31(22) 3555-3561. 

Monoamine oxidase (MAO) inhibitors block the oxidative deamination of monoamines, i.e. norepinephrine and serotonin by inhibiting monoamine oxidase type A (MAO-A) and dopamine also by monoamine oxidase type B (MAO-B) inhibition, thereby increasing these neurotransmittors at their receptors in the brain and in the periphery. MAO-A... 

J.F. Powell, P.P. Hau, W. Weyler, S. Chen, J. Salach, K. Adrikopoulos, J. Mallet, X.O. Breakefield, The primary structure of bovine monoamine oxidase type A Comparison with peptide sequences of bovine monoamine oxidase type B and other flavoenzymes, Biochem. J. 259 (1989) 407-413. 

Mechanism of Action An antiparkinson agent that irreversibly inhibits the activity of monoamine oxidase type B, the enzyme that breaks down dopamine, thereby increasing dopaminergic action. Therapeutic Effect Relieves signs and symptoms of Parkinson s disease. 

The side effects and cardiotoxicity of the tricyclic antidepressants have been discussed in detail elsewhere in this volume and, while there is ample evidence of their therapeutic efficacy, it seems difficult to justify their use, particularly in a group of patients who are most vulnerable to their detrimental side effects. Of the newer antidepressants, the reversible inhibitors of monoamine oxidase type A such as moclobemide may also be of value in the elderly depressed patient, particularly in those patients who fail to respond to the amine uptake inhibitor type of antidepressant. 

The drugs that can cause a serotonin syndrome when they are combined with SSRIs include monoamine oxidase inhibitors (including reversible inhibitors of monoamine oxidase types A and B), dextromethorphan,... 

Like moclobemide, toloxatone, a selective and reversible inhibitor of monoamine oxidase type A, is thought to be relatively safe in combination with sympathomimetics (SEDA-18, 16). However, sweating, tachycardia, and headache have been reported when terbutaline was added to toloxatone and phenylephrine (SEDA-18, 16). In healthy volunteers, doses up to 600 mg/day did not produce hypertensive reactions on challenge with oral tyramine (SEDA-17, 17). Two fatal cases of fulminant hepatitis have been reported (SEDA-16, 7). 

Finberg JPM, Pacak K, Kopin IJ, Goldstein DS (1993) Chronic inhibition of monoamine oxidase type-A increases noradrenaline release in rat frontal cortex. Naunyn-Schmied Arch Pharmacol 347i500-505. 

Monoamine oxidase type B inhibitors (rasagiline, selegiline) reduce the metabolism of dopamine by MAO-B. They are useful to delay disease progression in the early stages of the disease and as an adjunct to levodopa. 

FIGURE 31.6 PET scans showing dose dependency and time dependency of lazabemide inhibition of monoamine oxidase, type B in human brain. (Reproduced with permission from Fowler JS, Volkow ND, Wang G-J, Dewey SL. J Nucl Med 1999 40 1154-63.)... 

MAOIs increase the availability of noradrenaline and serotonin by preventing their destruction by the monoamine oxidase type A enzyme in the presynaptic terminal. The older MAOIs, phenelzine. 

Other substances that are being evaluated in Alzheimer s disease include the antioxidant vitamin E, the monoamine oxidase type B inhibitor, selegeline (see p. 425) and the plant extract gingko biloba, which is though to have antioxidant and cholinergic activity. Oestrogens and nonsteroidal anti-inflammatory agents may also have protective effects. 

The authors proposed that selegiline may have caused this effect by inhibiting dopamine metabolism, and that selegiline may not be as specific an inhibitor of monoamine oxidase type B as previously thought. 

Selegiline is a relatively selective and irreversible inhibitor of monoamine oxidase type B, which has been used in the treatment of Parkinson s disease. It was originally suggested that selegiline may be neuroprotective. However, in a prospective double-blind study no such action was seen (1). On the other hand, selegiline does delay the start of disability, determined by the need for levodopa and progression of parkinsonian signs and symptoms (2). 

As the authors pointed out, the selectivity of selegiline for monoamine oxidase type B may be less than was once thought, and co-administration of the drug with dopamine may be risky. 

Irreversibly inhibits monoamine oxidase type B activity. Increases dopaminergic action, assisting in reduction in tremor, akinesia (absence of sense of movement), posture and equilibrium disorders, rigidity of parkinsonism... 

Figure 12.3. Phenylpiperidine analgesics and metabolic activation of MPTP. In efforts to synthesize the meperidine-like analgesic agent MPPP ("designer heroin,") (4), MPTP (3)can be formed. It is converted selectively by monoamine oxidase type B (MAO-B, inhibited by agents including deprenyl (selegiline)and pargylineto MPDP (7), and thence to MPP" (8)the proposed toxic species that accumulated in dopamine neurons to result in disruption of their cellular respiration and death.

Mendlewicz J, Youdim MB (1983) L-Deprenil, a selective monoamine oxidase type B inhibitor, in the treatment of depression a double blind evaluation. Br J Psychiatry 142 508-511... 

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