Monoamine oxidase inhibitors reversible

Listing of antidepressants grouped by principal mechanism of action in the synapse. Abbreviations MAOI—irreversible = irreversible monoamine oxidase inhibitor MAOI—reversible = reversible monoamine oxidase inhibitor NDRl = norepinephrine/ dopamine reuptake inhibitor NRI = norepinephrine reuptake inhibitor NSRl = norepinephrine/serotonin reuptake inhibitor NSSA = norepinephrine/specific serotonin agonist SRI = serotonin reuptake inhibitor SRl/serotonin-2 blocker = serotonin reuptake inhibitor and serotonin-2 receptor antagonist. 

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. 

J. Wouters, F. Moureau, G. Vercauteren, G. Evrard, F. Durant, J.J. Koenig, F. Ducrey, F.X. Jarreau, Experimental and theoretical study of reversible monoamine oxidase inhibitors Structural approach of the active site of the enzyme, J. Neural. Transm. Suppi. 41 (1994) 313-319. 

I. J. Koenig, F.X. Jarreau, A reversible monoamine oxidase inhibitor, toloxatone structural and electronic properties, Eur. J. Med. Chem. 27 (1992) 939-948. 

Amrein R, Allen SR, Guentert TW, Hartmann D, Lorscheid T, Schoerlin MP, Vranesic D. The pharmacology of reversible monoamine oxidase inhibitors. Br J Psychiatry Suppl 1989 6 66-71. 

In the 1980s an entirely new class of antidepressant arrived with the SSRIs, firstly fluvoxamine immediately followed by fluoxetine (Prozac). Within 10 years, the SSRI class accounted for half of antidepressant prescriptions in the United Kingdom. Further developments in the evolution of the antidepressants have been novel compounds such as venlafaxine, reboxetine, nefazodone and mirtazapine, and a reversible monoamine oxidase inhibitor, moclobemide. 

Korn A, DaPrada M, Raffesberg W, Gasic S, Eichler HG. Effect of moclobemide, a new reversible monoamine oxidase inhibitor, on absorption and pressor effect oftyramine.JCorti-ovasc Pharmacol 9ZZ) 11, 17-23. 

Levodopa interacts with many different drugs. When levodopa is used with phenytoin, reserpine, and papaverine, there is a decrease in response to levodopa The risk of a hypertensive crisis increases when levodopa is used with the monoamine oxidase inhibitors (see Chap. 31). Foods high in pyridoxine (vitamin B6) or vitamin B6 preparations reverse the effect of levodopa However, when carbidopa is used with levodopa, pyridoxine has no effect on the action of levodopa hi fact, when levodopa and carbidopa are given together, pyridoxine may be prescribed to decrease the adverse effects associated with levodopa... 

Berlin, I.S.S., Spreux-Varoquaux, O., Launay, J.M., Olivares, R., Millet, V., Lecrubier, Y., Puech, A.J. A reversible monoamine oxidase A inhibitor (moclobemide) facilitates smoking cessation and abstinence in heavy, dependent smokers. Clin. Pharmacol. Ther. 58 444, 1995. 

A method has been described by which the effects of reversible competitive monoamine oxidase inhibitors might be estimated successfully ex vivo (Green, 1984). This method relies upon the ability of a reversible competitive inhibitor (perhaps administered chronically) to protect against the effects of an irreversible inhibitor (administered as a single dose) that binds to the enzyme active site. As inhibition by an irreversible inhibitor can be measured quite easily ex vivo, the degree of irreversible inhibition in an animal coadministered a reversible competitive inhibitor would be less than that in a control animal that received only the irreversible inhibitor. The difference would provide an estimate of the degree to which enzyme was bound (protected) by the reversible inhibitor in vivo. 

Monoamine Oxidase Inhibitors (MAOIs). Early studies also evaluated the effectiveness of the MAOl phenelzine. Phenelzine, relative to TCAs, provided greater benefit for PTSD however, its usefulness is limited by its potential for drug and food interactions. A recent open label study suggests that the reversible MAOI moclobemide might be helpful for PTSD. It is not available in the United States. 

Monoamine Oxidase inhibitors (MAOis). There are no controlled studies of MAOIs for the treatment of AN. In addition, the dietary restrictions imposed on patients taking this class of antidepressant and their propensity for lowering blood pressure makes their use in AN inadvisable. In the future, the issue of using MAOis may be reopened with the advent of the so-called reversible MAOis such as moclobemide that apparently do not require a tyramine-restricted diet. 

Monoamine Oxidase Inhibitors (MAOIs). The MAOls work in a unique fashion by blocking the activity of an enzyme that degrades each of three key brain transmitters norepinephrine, dopamine, and serotonin. These widespread effects on several brain transmitter systems make the MAOls a potentially very effective class of medications for a variety of disorders. A few small studies have evaluated the usefulness of the MAOls in the treatment of BPD and found them moderately helpful for the impulsivity associated with this illness. Unfortunately, the requirements for strict dietary restrictions due to a risk of hypertensive crisis severely limit the usefulness of MAOls in the treatment of BPD. These restrictions are a particular concern when treating patients who have problems with impulsivity and are therefore likely to have difficulty maintaining the dietary regimen. For this reason, although they may theoretically be helpful, MAOls should only be used to treat BPD after other more easily tolerated medications have been tried and have failed. In the near future, so-called reversible MAOls that appear to avoid the need for diet restrictions may become available. If so, this will allow us to reconsider their use in the treatment of BPD. For more information regarding the use of MAOls, please refer to Chapter 3. 

K. Yoshimi, M. Kozuka, J. Sakai, T. lizawa, Y. Shimizu, I. Kaneko, K. Kojima, N. Iwata, Novel monoamine oxidase inhibitors, 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, and their differential reversibility, Jpn. J. Pharmacol. 88 (2002) 174-182. 

Monoamine oxidase inhibitors (MAOIs) and reversible inhibitors... 

Monoamine oxidase inhibitors. The monoamine oxidase inhibitors (MAOIs) inhibit the intracellular catabolic enzyme monoamine oxidase. There are two types of monoamine oxidase MAO-A and MAO-B, both of which metabolize tyramine and dopamine. In addition, MAO-A preferentially metabolizes norepinephrine, epinephrine, and serotonin, and MAO-B preferentially metabolizes phenylethylamine (an endogenous amphetamine-like substance) and N-methylhistamine (Ernst, 1996). Some MAOIs are selective for A or B and some are nonselective (mixed). In addition, irreversible MAOIs (e.g., phenelzine, tranylcypromine) are more susceptible to the cheese effect than are the reversible agents (e.g., moclobemide). 

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. 

Bakish D The use of the reversible monoamine oxidase-A inhibitor brofaromine in social phobia complicated by panic disorder with agoraphobia. J Clin Psychopharmacol 14 74-75, 1994... 

Bakish D, Saxena BM, Bowen R, et al Reversible monoamine oxidase-A inhibitors in panic disorder. Clin Neuropharmacol 16 (suppl 2 S77-S82, 1993a Bakish D, Lapierre Y, Weinstein R, et al Ritanserin, imipramine and placebo in the treatment of dysthymic disorder. J Chn Psychopharmacol 13 409-414, 1993b Bakish D, Ravindran A, Hooper C, et al Psychopharmacological treatment response of patients with a DSM-111 diagnosis of dysthymic disorder. Psychopharmacol Bull 30 53-59, 1994... 

Montgomery SA, Brown RE, Clark M Economic analysis of treating depression with nefazodone v. imipramine. Br J Psychiatry 168 768-771, 1996 Monti JM Effect of a reversible monoamine oxidase-A inhibitor (moclobemide) on sleep of depressed patients. Br J Psychiatry Suppl 155 61-65, 1989 Monti JM, Alterwain P, Monti D The effects of moclobemide on nocturnal sleep of depressed patients. J Affect Disord 20 201-208, 1990 Montkowski A, Holsboer F Absence of cognitive and memory deficits in transgenic mice with heterozygous disrupt of the brain-derived neurotrophic factor gene. J Psychiatr Res [in press)... 

Reul JMHM, Labeur MS, Grigoriadis DE, et al Hypothalamic-pituitary-adrenocortical axis changes in the rat after long-term treatment with the reversible monoamine oxidase A inhibitor moclobemide. Neuroendocrinology 60 509-519, 1994a... 

Monoamine oxidase inhibitors MAO is found in neural and other tissues, such as the gut and liver. In the neuron, this enzyme functions as a "safety valve" to oxidatively deaminate and inacti vate any excess neurotransmitter molecules (norepinephrine, dopamine, or serotonin) that may leak out of synaptic vesicles when the neuron is at rest. The MAO inhibitors2 may irreversibly or reversibly inactivate the enzyme, permitting neurotransmitter molecules to escape degradation and, therefore, to both accumu late within the presynaptic neuron and to leak into the synaptic space. This causes activation of norepinephrine and serotonin receptors, and may be responsible for the antidepressant action of these drugs. 

FIGURE 5 — 15. Monoamine oxidase inhibitors act as antidepressants, since they block the enzyme MAO from destroying monoamine neurotransmitters, thus allowing them to accumulate. This accumulation theoretically reverses the prior neurotransmitter deficiency (see Fig. 5—14) and according to the monoamine hypothesis, relieves depression by returning the monoamine neuron to the normal state. 

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,... 

Interactions. Morphine (also pethidine and possibly other opioids) is potentiated by monoamine oxidase inhibitors. Any central nervous system depressant (including alcohol) will have additive effects. Patients recently exposed to neuromuscular blocking agents (unless this is adequately reversed, e.g. by neostigmine) are particularly at risk from the respiratory depressant effects of morphine. The effect of diuretic drugs may be reduced by release of antidiuretic hormone by morphine. Useful interactions include the potientating effect on pain relief of tricyclic antidepressants and of dexamfetamine. 

---