Serotonin monoamine oxidase

Considerable attention has been paid to the ultimate postsynaptic effects of increased neurotransmitters in the synapses. In tests of postsynaptic effects, cAMP concentrations have consistently decreased rather than increased, in spite of the presumably longer duration of action of the transmitters. In addition, the number of postsynaptic -adrenoceptors has shown a measurable decrease that follows the same delayed time course as clinical improvement in patients. Thus, the initial increase in neurotransmitter seen with some antidepressants appears to produce, over time, a compensatory decrease in receptor activity, ie, down-regulation of receptors. Decreases in norepinephrine-stimulated cAMP and in B-adrenoceptor binding have been conclusively shown for selective norepinephrine uptake inhibitors, those with mixed action on norepinephrine and serotonin, monoamine oxidase inhibitors, and even electroconvulsive therapy. Such changes do not consistently occur after the selective serotonin uptake inhibitors, 2 receptor antagonists, and mixed serotonin antagonists. 

Treatment of Major Depression. Dmgs commonly used for the treatment of depressive disorders can be classified heuristicaHy iato two main categories first-generation antidepressants with the tricycHc antidepressants (TCAs) and the irreversible, nonselective monoamine—oxidase (MAO) inhibitors, and second-generation antidepressants with the atypical antidepressants, the reversible inhibitors of monoamine—oxidase A (RIMAs), and the selective serotonin reuptake inhibitors (SSRIs). Table 4 fists the available antidepressants. 

Future Outlook for Antidepressants. Third-generation antidepressants are expected to combine superior efficacy and improved safety, but are unlikely to reduce the onset of therapeutic action in depressed patients (179). Many dmgs in clinical development as antidepressive agents focus on estabhshed properties such as inhibition of serotonin, dopamine, and/or noradrenaline reuptake, agonistic or antagonistic action at various serotonin receptor subtypes, presynaptic tt2-adrenoceptor antagonism, or specific monoamine—oxidase type A inhibition. Examples include buspirone (3) (only... 

Monoamine Oxidase Inhibitors. MAOIs inactivate the enzyme MAO, which is responsible for the oxidative deamination of a variety of endogenous and exogenous substances. Among the endogenous substances are the neurotransmitters, norepinephrine, dopamine, and serotonin. The prototype MAOI is iproniazid [54-92-2] (25), originally tested as an antitubercular dmg and a close chemical relative of the effective antitubercular, isoniazid [54-85-3] (26). Tubercular patients exhibited mood elevation, although no reHef of their tuberculosis, following chronic administration of iproniazid. In... 

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

The TCAs, such as amitriptyline (Elavil) and dox-epin (Sinequan), inhibit reuptake of norepinephrine or serotonin at the presynaptic neuron. Drug classified as MAOIs inhibit the activity of monoamine oxidase a complex enzyme system that is responsible for breaking down amines. This results in an increase in endogenous epinephrine, norepinephrine and serotonin in the nervous system. An increase in these neurohormones results in stimulation of the CNS. The action of the SSRIs is linked to their inhibition of CNS neuronal uptake of serotonin (a CNS neurotransmitter). The increase in serotonin levels is thought to act as a stimulant to reverse depression. 

Bogdanski, D.F. Weissbach, H. and Udenfriend, S. The distribution of serotonin, 5-hydroxytryptophan decarboxylase, and monoamine oxidase in brain. J Neurochem 1 272-278, 1957. 

Fuller, R.W. Serotonin oxidation by rat brain monoamine oxidase Inhibition by 4-chloroamphetamine. Life Sci 5 2247-2252, 1966. 

MAOa Monoamine oxidase type A NSAID non-steroidal anti-inflammatory drug SSRI selective serotonin reuptake inhibitors... 

Monoamine oxidase inhibition Serotonin reuptake inhibition Norepinephrine reuptake inhibition Dopamine reuptake inhibition a2-Adrenergic receptor blockade Serotonin-2A receptor blockade Serotonin-2C receptor blockade Serotonin-3 receptor blockade op-Adrenergic receptor blockade Histamine-1 receptor blockade Muscarinic cholinergic receptor blockade... 

MAOI, monoamine oxidase inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

MAOI, monoamine oxidase inhibitor SARI, serotonin antagonist and reuptake inhibitor SNRI, serotonin and norepinephrine reuptake inhibitor SSRI, selective serotonin reuptake inhibitor TCA, tricyclic antidepressant. 

Tricyclic antidepressants Monoamine oxidase inhibitors Selective serotonin reuptake inhibitors Antipsychotics Phenothiazines Risperidone Lithium... 

Dizziness, vertigo, nausea, vomiting, constipation, and lethargy are all relatively common adverse events. These effects are more pronounced for several days after initiation and following upward dose titration. Seizures have been reported rarely the risk is dose-related and appears to increase with concomitant use of antidepressants, such as tricyclic antidepressants or selective serotonin reuptake inhibitors. Tramadol should be avoided in patients receiving monoamine oxidase (MAO) inhibitors because tramadol inhibits the uptake of norepinephrine and serotonin. 

Cusin, C., Serretti, A., Zanardi, R. etal. (2002). Influence of monoamine oxidase A and serotonin receptor 2A polymorphisms in SSRI antidepressant activity. Int.. Neuropsychopharmacol, 5, 27-35. 

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. 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

Against this backdrop, researchers reported evidence that iproniazid, the antitubercular drug that was to become the first antidepressant, might increase norepinephrine and serotonin levels in the brain. How did it have this effect Recall that some of the neurotransmitter molecules released by a neuron are destroyed by enzymes in the synaptic cleft between the sending presynaptic neuron and the receiving postsynaptic neuron. When the neurotransmitter is a monoamine - like norepinephrine and serotonin - this process is called monoamine oxidase (MAO). As early as 1952 researchers at the Northwestern University Medical School in Chicago reported that iproniazid inhibited the oxidation of monoamines. This meant that iproniazid was a... 

Inhibition of monoamine oxidase has been proposed as a possible mechanism underlying the hydrogen sulfide-mediated disruption of neurotransmission in brain stem nuclei controlling respiration (Warenycia et al. 1989a). Administration of sodium hydrosulfide, an alkali salt of hydrogen sulfide, has been shown to increase brain catecholamine and serotonin levels in rats. It has also been suggested that persulfide formation resulting from sulfide interaction with tissue cystine and cystinyl peptides may underlie some... 

MAOI (Monoamine Oxidase Inhibitors) will intensify and prolong the effects of NN-DMT, however this is never recommended. Foolish combinations of MAOIs and other drugs can lead to serious health problems and even death. The tryptamines are normally metabolized by an MAO in the body. MAO metabolizes serotonin, norepinephrine, and dopamine. By inhibiting this, MAOIs increase levels of those neurotransmitters. Tyramine will not be metabolized and will cause an increase in tyramine levels in blood. 

Reserpine inhibits the synaptic vesicular storage of the monoamines dopamine, serotonin and noradrenaline. As a result they leak out into the cytoplasm where they are inactivated by monoamine oxidase this causes their long-lasting depletion. The resulting low levels of dopamine underlie the antipsychotic actions of reserpine (Chapter 11), whereas the reduced noradrenaline levels underlie its antihypertensive actions. Finally, the resulting low levels of serotonin and noradrenaline mean that reserpine also induces depression. These severe side effects mean that reserpine is no longer used clinically as a treatment for schizophrenia (Chapter 11). 

Inside the cytoplasm of the presynaptic neuron the monoamines are exposed to the mitochondrial outer membrane-bound enzyme monoamine oxidase (MAO). MAO breaks the monoamines down into inactive metabolites before they are taken up into the vesicles. However, if MAO is inhibited, then the monoamines enter the vesicles and are available for release. MAO inhibitors, such as moclobemide, have been used in the treatment of depression, since they increase the availability of noradrenaline and serotonin. Selegiline is used for Parkinson s disease, since it raises dopamine levels. 

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. 

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