Monoamine oxidase inhibitors, role

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

In an early study, Insel et al. [1983b] compared the efficacy of CMI with that of clorgiline, a monoamine oxidase-A inhibitor, in a controlled crossover study of patients with OCD. Although CMl was effective, patients on clorgiline did not improve at all. Vallejo et al. [1992] conducted a controlled clinical trial of the efficacy of CMl and phenelzine in 30 patients with OCD. The authors reported improvement in both groups however, the lack of a placebo control and the small size of the study groups limit the applicability of these findings. Further studies on the therapeutic role of monoamine oxidase inhibitors in OCD, especially in OCD with comorbid panic disorder, are warranted. 

Kennedy SH, Goldbloom DS, Ralevski E, et al. Is there a role for selective monoamine oxidase inhibitor therapy in bulimia nervosa A placebo-controlled trial of brofaromine. J Clin Psychopharmacoi 1993 13 415-422. 

Both of these materials, a-MT and a,N-DMT, are effective monoamine oxidase inhibitors. Both of these materials show some of the syndrome that has been described for the monoamineoxidase inhibitors of the beta-carboline family. It would be interesting to design and conduct a study into the role that either of these might play in promoting the oral activity of the materials of ayahuasca that are deaminated and thus deactivated when taken alone. This entire argument could and should embrace the methoxylated counterpart, a,N,0-TMS. I am not aware of any studied that have been made as to its deaminase enzymatic effectiveness, but it too fulfills that nausea, discomfort, un-psychedelic pattern shown here. The expected increase in potency due to the 5-methoxyl group is proper, making it a more potent compound than either of these two. Let s put it into the study as well. 

Monoamine oxidase inhibitors (MAOIs), which were amongst the first antidepressant drugs to be used clinically. They affect one or both of the brain monoamine oxidase enzymes that play a role in the metabolism of serotonin, noradrenaline, dopamine and adrenaline. MAOIs inhibit breakdown of the neurotransmitters important in determining mood, which results in the antidepressant effect. 

Adverse interactions of lithium with tricyclic antidepressants, SSRIs, and monoamine oxidase inhibitors have been reviewed (581). In reviews of antidepressants and the serotonin syndrome, a possible contributory role has been suggested for lithium, based on case reports with tricyclic antidepressants, SSRIs, trazodone, and venlafax-ine (204,582). 

Kennedy SH. Continuation and maintenance treatments in major depression the neglected role of monoamine oxidase inhibitors. J Psychiatry Neurosci 1997 22 127-31. 

Previous reports that some TCA and non-TCA, like Iprindol and mianserin, were inhibitors of histamine-sensitive adenylate cyclase from mammalian brain Iri vitro were confirmed for a wide range of antidepressants.22 xhe effect appeared to be mediated by H2-receptors but neither monoamine oxidase inhibitors (MAOI) nor selective serotonin (5-HT) uptake inhibitors were very effective. However, TCA also blocked histamine-stimulated cyclic GMP formation in cultured nerve cells by a mechanism which involved Hx-receptors.23 The relevance of these findings, and indeed of the role of histamine in the central nervous sytem, has still to be defined. 

Spector and Willoughby - have pointed out that the vascular changes in the acute inflammatory reaction may be due to the destruction of local vasoconstrictor substances such as adrenaline. Evidence in favour of this mechanism includes the observation that increased capillary permeability after thermal injury is suppressed by iproniazid and other monoamine oxidase inhibitors. Such inhibitors are known to inhibit the conversion of adrenaline, noradrenaline, 5-hydroxytryptamine and other amines to inactive metabolites. The authors provide evidence that the action of the monoamine oxidase inhibitors on capillary permeability is dependent on their anti-enzymic activity and not on some other unrelated property. Nevertheless, the evidence remains indirect an attempt to detect pressor amines in the plasma of burned animals was unsuccessful. The potentiating effect of bretylium and the antagonistic action of an adrenolytic substance, dibenamine, on the action of iproniazid suggest that it is local depots of adrenaline rather than noradrenaline or 5-hydroxytryptamine which are involved. Independent support for this suggested role of catecholamines... 

In view of the theories of Spector and Willoughby regarding the role of monoamine oxidase inhibitors in preventing the destruction of an adrenalinelike substance in tissue injury, it is not surprising that other workers have also found that these drugs inhibit inflammation. Thus iproniazid phosphate and... 

Serotonin, also known as 5-hydroxytryptamine (5-HT) is biosynthesized from tryptophan and is a neurotransmitter. Serotonin plays an important role in many behaviors including sleep, appetite, memory, and mood [52]. People with depressive disorders exhibit low levels of serotonin in the synapses. Protonated serotonin binds to a serotonin reuptake transporter protein, sometimes referred to as the serotonin transporter (SERT) and is then moved to an inward position on the neuron and subsequently released into the cjdoplasm. Selective serotonin reuptake inhibitors (SSRI) bind with high affinity to the serotonin binding site of the transporter. This leads to antidepressant effects by increasing extracellular serotonin levels which in turn enhances serotonin neurotransmission [53]. The SSRI class of antidepressants has fewer side effects than the monoamine oxidase inhibitors. 

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. 

Monoamine oxidases (MAOs) are mitochondrial membrane enzymes. These flavin-dependent enzymes are responsible for the oxidative deamination of numerous endogenic and exogenic amines (norepinephrine, serotonin, dopamine, etc.). MAO A and B take part in the regulation of these amines in many organs, such as the brain. The essential physiological role of these amines, especially in the central nervous system, has motivated the search for inhibitors of their catabolism in order to enhance the synaptic concentration of neuroamines. 

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