Inhibitors of monoamine oxidases

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. 

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. 

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 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. 

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

No importance of metabolic processes to the mechanism of action has yet been demonstrated. The phenethylamines generally are not good inhibitors of monoamine oxidase (MAO), although more active compounds may not be good substrates for this enzyme (MAO) (36). However, no extensive studies of phenethylamines have been reported, as either inhibitors or substrates of MAO. For... 

Harmala alkaloids are potent inhibitors of monoamine oxidase (Callaway and Grob 1998). Thus, if combined with other antidepressants, such as selective serotonin reuptake inhibitors, there is potential for serious side effects. Harmaline or its metabolites also cross the placental barrier (Okonmah et al. 1988). 

Catiline is a known inhibitor of monoamine oxidase and a central stimulant as an indirect sympathomimetic. It is found in anorectic products. 

Selegiline is a selective and irreversible inhibitor of monoamine oxidase B (MAO-B) as long as it is... 

J.P. Johnston, Some observations upon a new inhibitor of monoamine oxidase in brain tissue, Biochem. Pharmacol. 17 (1968) 1285-1297. 

I.A. McDonald, J.M. Lacoste, P. Bey, M.G. Palfreyman, M. Zreika, Enzyme-activated irreversible inhibitors of monoamine oxidase Phenylallylamine stmcture-activity relationships, J. Med. Chem. 28 (1985) 186-193. 

Nonselective and Irreversible Inhibitors of Monoamine Oxidase A and Monoamine Oxidase B... 

Some evidence indicates that social phobia responds to SSRls, and case reports and studies with fluoxetine [B. Black et al. 1992 Van Ameringen et al. 1993), fluvoxamine [Mendels et al. 1995), paroxetine [Pitts et al. 1996 Ringold 1994), and sertraline [Katzelnick et al. 1995) have reported positive results. Although the full details of these studies have not been published, it seems that SSRls might well prove, in due course, to be effective treatments for social phobia. At the moment, the only treatment licensed for social phobia is moclobemide, which is a reversible inhibitor of monoamine oxidase-A [Nutt and Montgomery 1996 Versiani et al. 1992), and it is possible that it... 

Two drugs belonging to the selective and reversible class of MAOls, moclobemide and brofaromine, have been studied for use in the treatment of social phobia. Both agents are selective inhibitors of monoamine oxidase-A,... 

Based on some intriguing case reports (Jenike et al. 1983), a trial with a monoamine oxidase inhibitor (MAOI) may be an option in OCD patients who have comorbid panic disorder. In a double-blind trial, both phenelzine and clomipramine were found to be effective in reducing symptoms in OCD, as reflected on two of four OC measures [Vallejo et al. 1992). None of the patients in this study had panic disorder. This study suggests that MAOIs may be helpful in some patients with OCD even in the absence of panic disorder. However, in an earlier comparison trial, clomipramine, but not the MAOI clorgiline, resulted in significant reduction in OC symptoms [Insel et al. 1983b). Additional studies are needed to evaluate the place of MAOIs (including the newer reversible inhibitors of monoamine oxidase A [RIMAs], such as moclobemide) in the pharmacotherapy of OCD. 

M. Strolin Benedetti, P. Dostert (1985). Stereochemical aspects of MAO interactions reversible and selective inhibitors of monoamine oxidase. Trends Pharmacol. Sci. 6 246-251. 

Reversible inhibitor of monoamine oxidase activity (RIMA). (Atypical agent. 

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