Monoamine oxidase inhibitors uses

Sibutramine is more effective than placebo with the most significant weight loss during the first 6 months of use. Dry mouth, anorexia, insomnia, constipation, increased appetite, dizziness, and nausea occur two to three times more often than with placebo. Sibutramine should not be used in patients with coronary artery disease, stroke, congestive heart failure, arrhythmias, or monoamine oxidase inhibitor use. 

Synergism - a potentiation or prolongation which results in much greater than expected effects. This could involve competitive substrates for an enzyme or receptor, decreased excretion, displaced plasma protein binding, etc. The analgesic propoxyphene (Darvon ) slows down the excretion of ethanol and so increases the depressant effects of the alcohol. Recall the example given earlier of the monoamine oxidase inhibitors used as antidepressants and the tyramine-containing foods which could precipitate a hypertensive crisis. 

Monoamine oxidase inhibitors (used in the treatment of bipolar disorder) should not be used with khat, as the combination may cause a potentially dangerous increase in blood pressure. 

Richard, A.J. and Kier, L.B. (1980). SAR Analysis of Hydrazide Monoamine Oxidase Inhibitors Using Molecular Connectivity. J.Pharm.ScL, 69,124. 

Some major classes include ACE inhibitors (used mainly as ANTIHYPERTENSIVE AGENTS). MONOAMINE-OXIDASE INHIBITORS (used mainly as ANTIDEPRESSANTS). ANTICHOLINESTERASES (used for a number of purposes). CARBONIC ANHYDRASE INHIBITORS, (used mainly as diuretics). PHOSPHODIESTERASE INHIBITORS (used as BRONCHODILATORS, CNS STIMULANTS, INOTROPIC AGENTS). 

Racemic deprenyl, a monoamine-oxidase inhibitor used in the treatment of depression, is metabolized to (+)- and ( )-metamphetamine, the former being much more active than its ( )-isomer as central stimulant leading to drug abuse (Table 26.7). 

The ingestion of ethylene glycol (antifreeze), iron tablets, monoamine oxidase inhibitors used for depressive disorders (eg, phenelzine), or verapamil can result in metabolic acidosis, with an increase in anion gap. The answer is (E),... 

Monoamine oxidase inhibitors used in depressive disorders (phenelzine, tranylcypromine) increase the stores of norepinephrine in sympathetic nerve endings. They also inhibit the metabolism of tyramine, which at high levels in the blood can act as an indirect sympathomimetic to release norepinephrine. The answer is (L). 

Tranylcypromine is a chiral monoamine oxidase inhibitor used in the treatment of depression. The drug is similar to mefloquine in that it is contains a diastereomeric structure but is only administered as the 50 50 combination of the (- -)-lS,2R and (—)-lR,2S species. The enantiomers possess differences in their pharmacological properties in that (-I-) tranylcypromine is much more effective than its antipode in MAO inhibition, but the (—) enantiomer causes greater diminution of catecholamine reuptake and release than (-I-) enantiomer [147]. With respect to its pharmacokinetics (Table 1), the (-I-) enantiomer seemed to be cleared via the oral route 4 to 8 times more rapidly than antipode based on significantly... 

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. 

These reactions, which have provided a means of inhibiting the flavin-linked monoamine oxidases, enable us to end on a clinical note. The monoamine oxidases are responsible for the deamination of monoamines such as adrenaline, noradrenaline, dopamine, and serotonin, which act as neurotransmitters. Imbalances in the levels of monoamines cause various psychiatric and neurological disorders Parkinson s disease is associated with lowered levels of dopamine, and low levels of other monoamines are associated with depression. Inhibitors of monoamine oxidases may consequently be used to treat Parkinson s disease and depression. The flavin moiety is covalently bound to the enzyme by the thiol group of a cysteine residue (equation 9.17). The acetylenic suicide inhibitor N,N-dimethyl-propargylamine inactivates monoamine oxidases by alkylating the flavin on N-5.25 A likely mechanism for the reaction is the Michael addition of the N-5 of the reduced flavin to the acetylenic carbon 2... 

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