Monamine oxidase

CgHjiN. Liquid, b.p. 79 C. Used as the hydrochloride, C HnN HCI, with m.p. 164°C. Tranylcypromine is an inhibitor of monamine oxidase and is administered orally in the treatment of depressive illness. 

The oxazoloquinoline 629 was obtained from 7-formyloxazoloquinoline 628 as shown in Scheme 107. The inhibition of monamine oxidase by 629 was studied (97FRP2737206). 

Incorporation of the phenethyl moiety into a carbocyclic ring was at first sight compatible with amphetamine-like activity. Clinical experience with one of these agents, tranylcypromine (79), revealed the interesting fact that this drug in fact possessed considerable activity as a monamine oxidase inhibitor and as such was useful in the treatment of depression. Decomposition of ethyl diazoacetate in the presence of styrene affords a mixture of cyclopropanes in which the trans isomer predominates. Saponification gives acid 77. Conversion to the acid chloride followed by treatment with sodium azide leads to the isocyanate, 78, via Curtius rearrangement. Saponification of 78 affords tranylcypromine (79). 

In the discussion of benzylamines, we have met medicinal agents that owe their activity to some particular functionality almost without reference to the structure of the rest of the molecule. The hydrazine group is one such function in that it frequently confers monamine oxidase-inhibiting activity to molecules containing that group. Such agents frequently find use as antidepressants. Thus, reduction of the hydrazone of phenyl-acetaldehyde (84) affords the antidepressant phenelzine (85). Similar treatment of the derivative of phenylacetone (86) gives pheniprazine (87). ... 

There is an increase in anticholinergic effects when antihistamines are administered with the monamine oxidase inhibitors (MAOIs) and additive sedative effects if administered with central nervous system depressants (eg, narcotic analgesics or alcohol). When cimetidine and loratadine are administered together there is a risk for increased loratadine levels. 

Antipsychotics, bromocriptine, carbamazepine, chlorpropamide, cyclophosphamide, desmopressin, ecstasy, lamotrigine, monamine oxidase inhibitors, NSAIDs, oxcarbazepine, oxytocin, tricyclic antidepressants, selective serotonin reuptake inhibitors, vasopressin, vinblastine, and vincristine... 

Here then is the logic behind the first version of the chemical-imbalance theory. Iproniazid is a monamine oxidase inhibitor - it inhibits the oxidation of norepinephrine and serotonin in the synapses, thereby leaving more of these neurotransmitters available in the brain. When depressed people take iproniazid, they get better. Therefore insufficient norepinephrine and/or serotonin causes depression.12... 

MAOI non-selective monoamine oxidase (A/B) inhibitors RIMA reversible inhibitor of monamine oxidase type A SSRI selective serotonin (5-HT) reuptake inhibitors SNRI serotonin/noradrenaline reuptake inhibitor SNARI selective noradrenaline (NA) reuptake inhibitor NA = 5-HT — DA potency of the drug is very similar in raising the level of both (or all three) monamines NA > 5-HT more selective for NA 5-HT>NA more selective for 5-HT NA increases the release of NA. 

Zl. Zeller, E. A., Some remarks about monamine oxidase and monoamine inhibitors. J. Neuropsychiat. Suppl. 1, 125-130 (1960). 

Xanthene oxidase Monamine oxidase Diamine oxidase Cytosol Mitochondria Cytosol... 

In order to increase the external validity of our models, it might be desirable to consider some nonnicotine ingredients of tobacco smoke. It appears that there are natural monamine oxidase (MAO) inhibitors in tobacco smoke (Lewis et al. 2007). It would be interesting to determine whether the coadministration of a low dose of a standard MAO inhibitor along with chronic nicotine would increase physical dependence, as assessed by various withdrawal measures, hi view of the antidepressant properties of MAO inhibitors, measures reflecting aspects of depression might be particularly affected. 

Hypersensitivity to maprotiline or mirtazapine coadministration with monamine oxidase inhibitors (MAOIs). 

Hypersensitivity to any component of this medication or to clonidine concurrent monamine oxidase inhibitor therapy. 

The role of amine oxidase in the inactivation of sympathomimetic amines rests on a much firmer basis. The enzymatic oxidative deamination of tyramine was described first by Hare (87). Kohn (105) partially purified it but the enzyme is widely distributed in mammalian tissues (30,109), is cyanide insensitive (15), and has resisted isolation. The name monamine oxidase has been suggested for the enzyme (154) referred to in the literature as tyramine oxidase, adrenaline oxidase (40), and aliphatic amine oxidase (128). 

FIGURE 27.6 The synthesis and actions of norepinephrine. MAO = monamine oxidase NE = norepinephrine DBH = dopamine a-hydroxylase. 

Scientists were looking for drugs to treat different medical problems when their observations almost accidentally led them to the study of depression and its treatment. Many scientists continued in this new direction to the discovery of the current three classifications of antidepressant drugs used today monamine oxidase... 

Monamine oxidase (MAO) inhibitors are antidepressants that can interact with sympathomimetic appetite depressants. Patients must discontinue using MAO inhibitors two weeks before taking these diet pills. Use of MAO inhibitors while taking anorectics will cause a sharp rise in blood pressure. 

Because of the dangerous adverse reactions (including the risk of death), individuals should not take methylphenidate if they have taken a class of drugs known as monamine oxidase (MAO) inhibitors within 14 days. Most MAO inhibitors are antidepressants, but some anti-tuberculosis drugs such as Ethambutol also have MAO effects. Since drug users are prone to many infectious diseases, it is not unheard of for drug abusers to come down with tuberculosis (TB). 

Simple xanthones include various mutagenic and antibacterial compounds such as bellidifolin (3-methoxy-l,5,8-trihydroxyxanthone). A number of simple xanthones are inhibitors of monamine oxidase A (bellidifolin, demethylbellidifolin, gentiacaulin, isogen-tisin and swerchirin), protein kinase (norathyriol) and of xanthine oxidase (athyriol, isoathyriol and norathyriol). 

Monamine oxidase inhibitors (MAOIs) Phenelzine (Nardil) Selegiline transdermal (Emsam) Tranylcypromine (Parnate)... 

Figure 10.3. Degradationof noradrenaline. COMT,Catechol-0-MethyItransferase MAO, and monamine oxidase. MAO initially forms an aldehyde (not shown) that is either reduced to an alcohol or oxidized to a carboxylic acid. Degradation of other catecholamines is analogous.

Figure 10.20. Stractures of cytotoxic catecholamine analogues, a 6-Hydroxdopa is converted to the cytotoxic metabolite 6-hy-droxydoapamine. b Methyli)henyl-tetrahydropyridine(MPTP) is formed as a byproduct of the synthetic opioid 1-methyl-l-phei rM-propionoxy-piperidine (MPPP). It is converted to the cytotoxic metabolite methyl hei rl-pyridinium, probably by monamine oxidase.

Figure 10.21. Mechanism of monamine oxidase (a), and its inhibition by tranylcypromine (b). The enzyme goes throngh a rad-icalic intermediate state, which may recombine with a radicalic conversion prodnct of the inhibitor. Accordingly, the inhibitor becomes bonnd covalently to the enzyme.

Lippman SB, Nash K. Monamine oxidase inhibitor update. Potential adverse food and drug interactions. Drtig Saf 1990 5 195-204. 

Bench CJ, Price GW, Lammertsma AA, Cremer JC, Luthra SK, Turton D, Dolan RJ, Kettler R, Dingemanse J, Da Prada M, Biziere K, McClelland GR, Jamieson VL, Wood ND, Frackowiak RSJ. Measurement of human cerebral monamine oxidase type B (MAO-B) activity with positron emission tomography (PET) A dose ranging study with the reversible inhibitor Ro 19-6327. Br J Clin Pharmacol 1991 40 169-73. 

Monamine oxidase— An enzyme found in the brain and liver which breaks down catecholamines such as norepinephrine, serotonin and dopamine. 

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