Pharmacology monoamine oxidase

Isoproterenol is given sublingually or by iv. It is metabolized by monoamine oxidase and catechol-0-methyltransferase in brain, Hver, and other adrenergically innervated organs. The pharmacological effects of isoproterenol are transient because of rapid inactivation and elimination. About 60% is excreted unchanged. Adverse effects using isoproterenol therapy include nervousness, hypotension, weakness, dizziness, headache, and tachycardia (86). 

Pharmacologically useful isoxazoles (B-82MI41600) include antibacterial sulfonamides (614), (615) and (616), semisynthetic penicillins (617), (618), (619) and (620), semisynthetic cephalosporin (621), anabolic steroid (622), the monoamine oxidase inhibitor (623) (used in psychotherapy), antiinflammatory agent (624) and antitumor agent (625). 

Nicotra A, Parvez SH, Glover V et al (eds) (2004) Monoamine oxidases molecular, pharmacological and neurotoxicological aspects a tribute to Prof. Merton Sandler. Neurotoxicology 25(1-2) 1-338 (January 2004)... 

Youdim MBH, Finberg JPM, Tipton KF (1988) Monoamine oxidases. In Trendelenburg U and Weiner N (eds) Catecholamines. II Handbook of experimental pharmacology. Springer Verlag, Berlin, pp 121-197... 

The synthesis and metabolism of trace amines and monoamine neurotransmitters largely overlap [1]. The trace amines PEA, TYR and TRP are synthesized in neurons by decarboxylation of precursor amino acids through the enzyme aromatic amino acid decarboxylase (AADC). OCT is derived from TYR. by involvement of the enzyme dopamine (3-hydroxylase (Fig. 1 DBH). The catabolism of trace amines occurs in both glia and neurons and is predominantly mediated by monoamine oxidases (MAO-A and -B). While TYR., TRP and OCT show approximately equal affinities toward MAO-A and MAO-B, PEA serves as preferred substrate for MAO-B. The metabolites phenylacetic acid (PEA), hydroxyphenylacetic acid (TYR.), hydroxymandelic acid (OCT), and indole-3-acetic (TRP) are believed to be pharmacologically inactive. 

Trace Amines. Figure 1 The main routes of trace amine metabolism. The trace amines (3-phenylethylamine (PEA), p-tyramine (TYR), octopamine (OCT) and tryptamine (TRP), highlighted by white shading, are each generated from their respective precursor amino acids by decarboxylation. They are rapidly metabolized by monoamine oxidase (MAO) to the pharmacologically inactive carboxylic acids. To a limited extent trace amines are also A/-methylated to the corresponding secondary amines which are believed to be pharmacologically active. Abbreviations AADC, aromatic amino acid decarboxylase DBH, dopamine b-hydroxylase NMT, nonspecific A/-methyltransferase PNMT, phenylethanolamine A/-methyltransferase TH, tyrosine hydroxylase. 

Synergy of unwanted pharmacological effect ginseng and its products will inhibit the central nervous system (CNS) when they are applied with luminal, chloral hydrate, or ephedrine, which can increase the release of dopamine, noradrenaline, and serotonin in the CNS thus inducing a hypertensive crisis if monoamine oxidase inhibitors (MAOIs) are given simultaneously. 

When Schildkraut introduced the monoamine theory of depression, he admitted that there was little direct evidence for it. Instead, it was based on the supposed effectiveness of antidepressant medication and the mistaken belief that reserpine makes people depressed. Schildkraut acknowledged that Most of this evidence is indirect, deriving from pharmacological studies with drugs such as reserpine, amphetamine and the monoamine oxidase inhibitor antidepressants which produce affective changes. 21 A half-century has passed since his chemical-imbalance theory of depression was introduced, and the presumed effectiveness of antidepressants remains the primary evidence in its support. But as we have seen, the therapeutic effects of antidepressants are largely due to the placebo effect, and this pretty much knocks the legs out from under the biochemical theory. 

Monamines are inactivated into aldehydes by amine oxidase (monoamine oxidase, MAO ) with deamination and simultaneous oxidation. MAO inhibitors therefore play an important role in pharmacological interventions in neurotransmitter metabolism. 

Pharmacology Tetracyclics enhance central noradrenergic and serotonergic activity. They do not inhibit monoamine oxidase. Although maprotiline and mirtazapine are in the same chemical class, they each affect different neurotransmitters and thus have different side effect profiles. Maprotiline primarily acts by blocking reuptake of norepinephrine at nerve endings. 

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. 

Pharmacology Selegiline hydrochloride is a levorotatory acetylenic derivative of phenethylamine. Although the mechanism of action is not fully understood, inhibition of monoamine oxidase (MAO) type B activity is of primary importance and selegiline... 

Pharmacokinetics Phenylephrine is irregularly absorbed from and readily metabolized in the GI tract. After IV administration, a pressor effect occurs almost immediately and persists for 15-20 minutes. After IM administration, a pressor effect occurs within 10-15 minutes and persists for 50 minutes to 1 hour. After oral inhalation of phenylephrine in combination with isoproterenol, pulmonary effects occur within a few minutes and persist for about 3 hours. The pharmacologic effects of phenylephrine are terminated at least partially bythe uptake of the drug into the tissues. Phenylephrine is metabolized in the liver and intestine by the enzyme monoamine oxidase (MAO). The metabolites and their route and rate of excretion have not been identified. 

SRls are currently the most prevalent pharmacological treatment used for panic disorder [see Westenberg and Den Boer, Chapter 24, in this volume], even though tricyclic antidepressants, monoamine oxidase inhibitors [MAOls], and benzodiazepines are also effective. The efficacy of the SRI antidepressants and the observation that initially they may induce deterioration of symptoms [which is usually not the case with treatment of depressed patients with the same medications] raise issues related to the pathobiology of anxiety and its comorbidity with depression. 

This was put forward in 1965 by J. Schildkraut and states that some, if not all, depressions are the consequence of an absolute or relative deficiency of catecholamines, particularly norepinephrine, at functionally important adrenergic receptor sites in the brain (Schildkraut, 1965, p. 509). The evidence brought forward in support of this hypothesis was impressive (Table 4.2) because it covered both clinical and multifarious pharmacological findings. The antidepressant effect of imipramine and of the monoamine oxidase (MAO) inhibitors was attributed to the fact that these medicaments bring about an increased supply of functionally available catecholamines at the synapse ... 

Robinson D, Kurtz W. Monoamine oxidase inhibiting drugs pharmacologic and therapeutic issues. In Meltzer H, ed. Psychopharmacoiogy the third generation of progress. New York Raven Press, 1987. 

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). 

Pharmacologic doses of pyridoxine (vitamin B6 ) enhance the extracerebral metabolism of levodopa and may therefore prevent its therapeutic effect unless a peripheral decarboxylase inhibitor is also taken. Levodopa should not be given to patients taking monoamine oxidase A inhibitors or within 2 weeks of their discontinuance because such a combination can lead to hypertensive crises. 

Pharmacologic strategies for dopaminergic therapy of Parkinson s disease. Drugs and their effects are highlighted (see text). MAO, monoamine oxidase COMT, catechol-O-methyltransferase DOPAC, dihydroxyphenylacetic acid L-DOPA, levodopa 3-OMD, 3-0-methyldopa. 

In this chapter, we will review pharmacological concepts underlying the use of several classes of antidepressant drugs, including the classical monoamine oxidase (MAO) inhibitors, the classical tricyclic antidepressants, the popular serotonin selective reuptake inhibitors (SSRIs), and the new selective noradrenergic reuptake... 

This material is intimately related to tranylcypromine, a clinically proven antidepressant. This drug is a known monoamine oxidase inhibitor, and it is certainly possible that some of this pharmacological property might be found in... 

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