Monoamine oxidase inhibitors indications

Urine catecholamines may also serve as biomarkers of disulfoton exposure. No human data are available to support this, but limited animal data provide some evidence of this. Disulfoton exposure caused a 173% and 313% increase in urinary noradrenaline and adrenaline levels in female rats, respectively, within 72 hours of exposure (Brzezinski 1969). The major metabolite of catecholamine metabolism, HMMA, was also detected in the urine from rats given acute doses of disulfoton (Wysocka-Paruszewska 1971). Because organophosphates other than disulfoton can cause an accumulation of acetylcholine at nerve synapses, these chemical compounds may also cause a release of catecholamines from the adrenals and the nervous system. In addition, increased blood and urine catecholamines can be associated with overstimulation of the adrenal medulla and/or the sympathetic neurons by excitement/stress or sympathomimetic drugs, and other chemical compounds such as reserpine, carbon tetrachloride, carbon disulfide, DDT, and monoamine oxidase inhibitors (MAO) inhibitors (Brzezinski 1969). For these reasons, a change in catecholamine levels is not a specific indicator of disulfoton exposure. 

Bromocriptine is a dopamine agonist acting by direct stimulation of the dopamine receptors. In Parkinson s disease, it is reserved for use in patients who are intolerant to levodopa or in whom levodopa alone is not sufficient. Orphenadrine is an antimuscarinic indicated in Parkinson s disease. Antimuscarinics tend to be more effective than levodopa in targeting tremor rather than rigidity and bradykinesia. Moclobemide is an antidepressant referred to as a reversible monoamine oxidase inhibitor (RIAAA) type A. 

Lorazepam is a short-acting benzodiazepine indicated for use in relieving anxiety and insomnia. Lorazepam may also be administered perioperatively to alleviate pain and in status epilepticus. Imipramine is a tricyclic antidepressant, paroxetine is a selective serotonin re-uptake inhibitor, venlafaxine is a serotonin and adrenaline re-uptake inhibitor and moclobemide is a reversible monoamine oxidase inhibitor. Imipramine, paroxetine, venlafaxine and moclobemide are all classified as antidepressants. 

Maintenance/Continuation/Extended treatment There is no evidence to indicate how long the depressed patient should be treated with nefazodone. However, it is generally agreed that pharmacologic treatment for acute episodes of depression should continue for at least 6 months. Whether the dose of antidepressant needed to induce remission is identical to the dose needed to maintain euthymia is unknown. In clinical trials, more than 250 patients were treated for at least 1 year. Switching to or from a monoamine oxidase inhibitor (MAOi) At least 14 days should elapse between discontinuation of an MAOI and initiation of therapy with nefazodone. In addition, wait at least 7 days after stopping nefazodone before starting an MAOI. 

Examples of monoamine oxidase inhibitors are phenelzine, tranylcypromine, isocarboxazid and mo-clobemide. They are indicated for atypical depression. Changes in the neurotransmitter levels are seen in several days but the clinical effect may lag by several weeks. Phenelzine is a non-selective hydrazine-type monoamine oxidase inhibitor while the also non-selective inhibitor tranylcypromine is of the non-hydrazine-type. Phenelzine, tranylcypromine and isocarboxazid are irreversible inhibitors. Phenelzine is partly metabolized by acetylation and slow acetylators are more prone to toxicity. It has anxiolytic properties and superior efficiacy in treating severe anxiety. 

TCA, tricyclic antidepressant SSRI, selective serotonin reuptake inhibitor MAOI, monoamine oxidase inhibitor. 0, no effect +, + +, + + + indicate increasing effect. 

Although behavioral treatments for social phobia have been well studied, there are very limited data on its pharmacological management, b- Blockers (propranolol, atenolol) have been recommended, but available evidence indicates their effect may be no different than that of placebo ( 78). In a controlled study, the monoamine oxidase inhibitor (MAOl) phenelzine has been shown to be more effective than placebo (78, 79). Anecdotal reports have also described efficacy with alprazolam, clonidine, and fluoxetine, but systematic data are lacking (80, 81, 82 and 83). 

Isocarboxazid is an MAO inhibitor, which blocks activity of enzyme MAO, thereby increasing monoamine (e.g., epinephrine, norepinephrine, serotonin) concentrations in CNS. It is indicated in the treatment of depression. Isocarboxazid (30 mg/kg) is a monoamine oxidase inhibitor (MAO) indicated for the treatment of depressed patients who have become refractory to tricyclic antidepressants... 

Siberian ginseng is specifically indicated for people with immunode-pression, fatigue, and a lack of vitality and perhaps those who get sick a lot. Unlike echinacea, it is not an immune stimulant rather, it is an immune enhancer and helps restore optimum functioning in the immune system. As it is a monoamine oxidase inhibitor, it is also useful in depression, a condition that often accompanies a severely depleted immune system. 

Dopamine is formed within the brain from both L-dopa and l-3-O-methyldopa, but the latter is probably demethylated first. Administration of either amino acid to man or to animals [487, 494,499] enhances brain levels of dopamine and noradrenaline, and of their O-methylated metabolites, the former effect being further enhanced by monoamine oxidase inhibitors and inhibitors of catechol 0-methyl transferase. Cerebral 3-O-methyldopamine arises by methylation of dopamine rather than by decarboxylation of L-3-O-methyldopa, while the increases in cerebral and urinary homovanillic acid levels after L-dopa arise by oxidative deamination and 3-O-methylation of dopamine formed at the periphery and the neuron. The accumulation of the long-lived amino acid, L-3-O-methyldopa, in the brain, and its slow conversion to dopamine, may well explain why the therapeutic effects of L-dopa in Parkinsonism disappear only slowly upon discontinuation of treatment. Indeed, preliminary studies in man [494] indicate that l-3-O-methyldopa exerts a therapeutic action in Parkinsonism without the com-comitant side effects normally associated with L-dopa therapy. The relevant information regarding the fate and mode of action of L-dopa in the central nervous system is summarised in Figure 5.8. 

The increase of monoacetylcadaverine and monopropionylcadaverine in blood could be caused by a higher rate of acetylation, or by a lowered catabolism of monoacylcadaverines. It is probable that monoacetylcadaverine and monopropiohylcadaverine are substrates for monoamine oxidases because their four-carbon analog (mono-acetylputrescine) is metabolized by monoamine oxidase in the rat (15). To test this assumption, we have measured brain concentrations of monoacylcadaverines in mice treated with monoamine oxidase inhibitors. The results in Table IV indicate that monoacetylcadaverine and monopropionylcadaverine are indeed the substrates for monoamine oxidases in the mouse brain. 

Fig. 1. Influence of substituents in the aromatic ring on the selectivity of 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives as monoamine oxidases (MAO) A or B inhibitors. Ratio of selectivity was calculated from IC50 values of MAO A and B determined by an in vitro assay of mouse brain mitochondria using 5-hydroxy tryptamine (5-HT) and 2-phenylethylamine (PEA) as specific substrates, respectively (see Ref. [9]). Smaller values indicate that inhibitors are MAO A selective [71].

Fig. 2. isozyme seiectivity of fluoroaiiyi amine monoamine oxidases (MAO) inhibitors. The seiectivity ratio was defined as the ratio of the concentrations of inhibitors required to decrease the activity of both forms of the enzyme at the same rate [77]. A high ratio thus indicates a B-seiective inhibitor. 

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... 

---