Of monoamine oxidase

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

Reversible Inhibitors of Monoamine Oxidase. Selective MAO-A inhibitors, which aie leveisible (so-called RIMAs), have also been developed, theiefoie substantially leduciag the potential foi food and dmg iateiactions. Indeed, the tyiamine-potentiating effects of these dmgs is much reduced compared with the irreversible MAO inhibitors. The RIMAs represent effective and safer alternatives to the older MAO inhibitors. The only marketed RIMAs ate toloxatone [29218-27-7] and moclobemide (55). The latter is used widely as an effective, weU-tolerated antidepressant. 

Oxazolidinones and dihydrofuranones as inactivators and substrates of monoamine oxidase B, approaches to the design of antiparkinsonian agents 97F343. 

Monoamine Oxidases and their Inhibitors. Table 2 Kinetic parameters of the two forms of monoamine oxidase... 

Youdim MB, Edmondson D, Tipton KF (2006) The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 7(4) 295-309... 

MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

The amphetamines and the anorexiants should not be given during or within 14 days after administration of monoamine oxidase inhibitors (see Chap. 31) because the patient may experience hypertensive crisis and intracranial hemorrhage. When guanethidine is administered with the amphetamines or the anorexiants, the antihypertensive effect of guanethidine may decrease. Coadministration of the amphetamines or the anorexiants with the tricyclic antidepressants may decrease the effects of the amphetamines or the anorexiants. 

The TCAs, such as amitriptyline (Elavil) and dox-epin (Sinequan), inhibit reuptake of norepinephrine or serotonin at the presynaptic neuron. Drug classified as MAOIs inhibit the activity of monoamine oxidase a complex enzyme system that is responsible for breaking down amines. This results in an increase in endogenous epinephrine, norepinephrine and serotonin in the nervous system. An increase in these neurohormones results in stimulation of the CNS. The action of the SSRIs is linked to their inhibition of CNS neuronal uptake of serotonin (a CNS neurotransmitter). The increase in serotonin levels is thought to act as a stimulant to reverse depression. 

Medvedev AE, Veselovsky AV, Shvedov VI, Tikhonova OV, Moskvitina TA, Fedotova OA, et al. Inhibition of monoamine oxidase by pirlindole analogues 3D-QSAR and CoMFA analysis. / Chem Inf Comput Sci 1998 38 1137-44. Miller JR, Edmondson DE. Structure-activity relationships in the oxidation of para-substituted benzylamine analogues by recombinant human liver monoamine oxidase A. Biochemistry 1999 38 13670-83. 

Edmondson DE, Mattevi A, Binda C, Li M, Hubalek F. Structure and mechanism of monoamine oxidase. Curr Med Chem 2004 11 1983-93. 

Binda C, Hubalek E, Li M, Herzig Y, Sterling J, Edmondson DE, et al. Crystal structures of monoamine oxidase B in complex with four inhibitors of the V-propargylaminoindan class. J Med Chem 2004 47 1767-74. 

Lenders, JWM, Eisenhofer, G, Abeling, NGGM et al. (1996) Specific genetic deficiencies of the A and B isoenzimes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes. J. Clin. Invest. 97 1010-1019. 

Neff, NH and Costa, E (1966) The influence of monoamine oxidase inhibition on catecholamine synthesis. Life Sci. 5 951-959. 

Benedetti, M, Boucher, T, Carlsson, A and Fowler, CJ (1983) Intestinal metabolism of tyramine by both forms of monoamine oxidase in the rat. Biochem. Pharmacol. 32 47-52. 

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. 

Tyrer, P (1979) Clinical use of monoamine oxidase inhibitors. In Psychopharmacology of Affective Disorders (Eds Paykel, ES and Coppen, A), Oxford University Press, Oxford, pp. 159-178. 

Chakrabarti SK, Loua KM, Bai C, Durham H, Panisset JC. 1998. Modulation of monoamine oxidase activity in different brain regions and platelets following exposure of rats to methyhnercury. Neurotoxicol Teratol 20 161-168. 

It is premature to define the exact mechanism by which DA is involved in the response to METH or MDMA. It is known- that these drugs release large quantities of DA and that DA can be readily oxidized to reactive metabolites, which could possibly cause destruction of nerve terminals (Graham 1978 Maker et al. 1986). Moreover, these effects could be enhanced by inhibition of monoamine oxidase, which is known to occur with these drugs (Susuki et al. 1980). The possibility that 6-DOHA is formed and subsequently destroys the nerve terminals, as suggested by Seiden and Vosmer (1984), also requires investigation. 

The reversible inhibitors of monoamine oxidase (RIMAs) brofaramine and meclobemide have been studied with mixed results.48 Neither is approved for use in the United States, but they are available in Canada. 

Cusin, C., Serretti, A., Zanardi, R. etal. (2002). Influence of monoamine oxidase A and serotonin receptor 2A polymorphisms in SSRI antidepressant activity. Int.. Neuropsychopharmacol, 5, 27-35. 

Inhibition of monoamine oxidase has been proposed as a possible mechanism underlying the hydrogen sulfide-mediated disruption of neurotransmission in brain stem nuclei controlling respiration (Warenycia et al. 1989a). Administration of sodium hydrosulfide, an alkali salt of hydrogen sulfide, has been shown to increase brain catecholamine and serotonin levels in rats. It has also been suggested that persulfide formation resulting from sulfide interaction with tissue cystine and cystinyl peptides may underlie some... 

Perez, N. M. Benedito, M. A. (1997). Activities of monoamine oxidase (MAO) A and B in discrete regions of rat brain after rapid eye movement (REM) sleep deprivation. Pharmacol. Biochem. Behan. 58, 605-8. 

Tago, H., Kimura, H., Kitahama, K. et al. (1984). Cortical projections of monoamine oxidase-containing neurons from the posterior hypothalamus in the rat. 

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

The actions of dopamine are terminated through presynaptic reuptake. Some of the dopamine is then re-incorporated into vesicles, while the rest is metabolized (Fig. 46-3). Dopamine and its O-methyl derivative are both subject to the action of monoamine oxidase (MAO),... 

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