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The history of irreversible non-selective MAOI antidepressants in the USSR and Russia is systemized. The history of representatives’ appearance is described. The history of the study of pharmacological effects is highlighted. The history of the study of clinical effects in various mental disorders is analyzed in chronological order. The history of use in somatic pathology is summarized. The history of the use of special pharmaceutical forms is considered. The history of new experimental compounds creation is submitted. The features of history of irreversible non-selective MAOI antidepressants in the USSR and Russia in comparison with their history in other countries are characterized.

Context Research interest in monoamine oxidase (MAO) as a promising drug target for neurodegenerative diseases has a long history. However, efforts to develop MAO inhibitors (MAOIs) from marine sources have been limited, despite the increasing number of interesting marine natural products. Objective To review the potential of marine natural products as MAOIs source, including their activities and selectivity on MAO. Methods Public databases such as SciFinder, MarinLit and PubMed were systematically searched from 1991 until Dec 2019. MAO and MAOI were the key terms searched combined with marine natural products and marine. Results Six classes of marine natural products with good selectivity between the two MAO subtypes were organized with their selectivity and sources. Conclusions This is the first review to investigate the potential of marine natural products as MAOIs source. Despite the small number of known MAOIs from marine sources, marine natural products are potential leads for the further development of MAOI drugs with novel chemical frames and good selectivity.

Research interest in monoamine oxidase (MAO) as a promising drug target for neurodegenerative diseases has a long history. However, efforts to develop MAO inhibitors (MAOIs) from marine sources have been limited, despite the increasing number of interesting marine natural products. To review the potential of marine natural products as MAOIs source, including their activities and selectivity on MAO. Public databases such as SciFinder, MarinLit and PubMed were systematically searched from 1991 until Dec 2019. MAO and MAOI were the key terms searched combined with marine natural products and marine. Six classes of marine natural products with good selectivity between the two MAO subtypes were organized with their selectivity and sources. This is the first review to investigate the potential of marine natural products as MAOIs source. Despite the small number of known MAOIs from marine sources, marine natural products are potential leads for the further development of MAOI drugs with novel chemical frames and good selectivity. [ABSTRACT FROM AUTHOR]

Background: Unipolar major depression is commonly encountered in everyday clinical practice, especially in the primary-care setting. Its presentation is very variable, making missed diagnoses a common occurrence; with much dire consequence (e.g. suicide), careful examination of suspected cases and correct identification of affected patients becomes ever so important, not only to specialists but also to general practitioners, whom the majority of cases will present to. Unipolar major depression is a chronic, lifelong disease with a high recurrence rate and worsening prognosis with repeated episodes; therefore, appropriate, timely management in addition to patient education and guidance of their expectation is key to improving clinical outcomes and patient satisfaction. Methodology: The PubMed database and the MeSH tool were employed to collect the articles used in this review. Relevant articles were obtained, if possible, and reviewed. Objectives: Our goal was to perform a comprehensive review of recent review articles that examined unipolar major depression in adults in addition to etiology, epidemiology, pathogenesis, clinical features and types, diagnosis, management, or prognosis. Conclusion: Unipolar major depression is a common mental health problem presenting to the primary-care setting, with many missed diagnoses due to heterogenous presenting features. Management options include psychological therapy, pharmacological therapy, or a combination of both. Early detection and treatment considerably improve the clinical outcome; therefore, it's imperative that physicians, whether specialists or general practitioners, familiarize themselves with its clinical picture. [ABSTRACT FROM AUTHOR]

Many patients are prescribed antidepressants. This article discusses depression, as well as the available first- and second-line prescription medications used to manage the disorder in adults. [ABSTRACT FROM AUTHOR]

A group of N-malonyl-1,2-dihydroisoquinoline derivatives were synthesized and investigated as brain specific and shelf-stable MAO inhibitors. N-malonyl-1,2-dihydroisoquinoline redox carrier system was linked through amidic bond to 4-chloro and 4-nitrobenzylidenehydrazines ( 9a-b ), as monoamine oxidase inhibitors (MAOIs), and β-phenethylamine ( 14 ), as a model drug, to afford a novel group of N-malonyl-1,2-dihydroisoquinoline chemical delivery systems (DHIQCDSs) ( 13a-b and 18 ). These systems are expected to be stable against air oxidation due to the presence of the carbonyl group close to nitrogen of the dihydroisoquinoline. The synthesized DHIQCDS ( 18 ) was subjected to various chemical and biological investigations to evaluate its stability and prove its ability to cross the blood brain barrier and “lock-in” the brain. The in vitro chemical and enzymatic oxidation studies showed reasonable stability and adequate rate of conversion of DHIQCDS ( 18 ) to its corresponding quaternary metabolites. In vivo distribution study in rats revealed preferential concentration of the active moiety in the brain. Moreover, compounds ( 9a-b, 12a-b and 17 ) were screened for their in vitro MAO inhibitory activity compared to clorgyline as a reference compound. The inhibition profile was found to be competitive for both MAO-A and MAO-B isozymes with more selectivity toward MAO-A. Molecular docking study of compounds ( 9a-b, 12a-b and 17 ) and the suggested metabolites was carried out on both MAO-A and MAO-B isozymes. Observation of the docked poses revealed many interactions with many residues previously reported to have an effect on the inhibition of MAO enzyme. [ABSTRACT FROM AUTHOR]

Thirty seven novel 2-pyrazoline-1-ethanone derivatives were designed, synthesized and evaluated as selective hMAO inhibitors. Among them, compounds 7h (IC 50 = 2.40 μM) and 12c ( IC 50 = 2.00 μM ) exhibited best inhibitory activity and selectivity against hMAO-A, surpassing that of the positive control Clorgyline (IC 50 = 2.76 μM). Based on selective activity of hMAO-A, SAR analysis showed that the order of N1 substituent contribution was bromo ( 3 ) > piperidinyl ( 4 ) > morpholinyl ( 5 ) > imidazolyl ( 6 ), and compounds with electron-withdrawing substituents (-F, -Cl) at C3 or C5 phenyl ring of 2-pyrazoline nucleus dedicated stronger MAO-A inhibitory activity. Molecular docking showed that compounds 7h and 12c were nicely bound to hMAO-A via two hydrogen bonds (SER209, GLU216), one Pi–Pi interaction and three hydrogen bonds (SER209, GLU216, TYR69), one Sigma–Pi interaction, respectively. In addition, the substituent at C3 position of 2-pyrazoline with the N1 acetyl has little effect on MAO-A inhibitory activity. These data support further studies to assess rational design of more efficiently selective hMAO inhibitors in the future. [ABSTRACT FROM AUTHOR]

Abstract: With the aim to find out the structural features for the MAO inhibitory activity and selectivity, in the present communication we report the synthesis and pharmacological evaluation of a new series of bromo-6-methyl-3-phenylcoumarin derivatives (with bromo atom in both different benzene rings of the skeleton) with and without different number of methoxy substituent at the 3-phenyl ring. The methoxy substituents were introduced, in this new scaffold, in the meta and/or para positions of the 3-phenyl ring. The synthesized compounds 3–7 were evaluated as MAO-A and B inhibitors using R-(−)-deprenyl (selegiline) and iproniazide as reference inhibitors, showing, most of them, MAO-B inhibitory activities in the low nanomolar range. Compounds 4 (IC50 =11.05nM), 5 (IC50 =3.23nM) and 6 (IC50 =7.12nM) show higher activity than selegiline (IC50 =19.60nM) and higher MAO-B selectivity, with more than 9050-fold, 30,960-fold and 14,045-fold inhibition levels, with respect to the MAO-A isoform. [ABSTRACT FROM AUTHOR]

Stewart et al (2009) have outlined the evidence in support of the validity of the DSM-IV definition of the ‘With Atypical Features’ episode specifier. Although recognizing the historical significance and clinical utility of the concept of atypical depression, this article takes issue with the DSM-IV criteria. It is concluded that mood reactivity, the A or obligative criterion, is neither significantly associated with the other symptomatic criteria nor useful to diagnose atypical depression, and thus should be eliminated. Problems with operationalization, specification, and reliability of ratings of the diagnostic criteria further limit validity. Despite these limitations in classification, many of the features associated with atypical depression are linked to an early onset of affective illness, including trait-like interpersonal sensitivity, comorbid social anxiety and agoraphobia, a history of childhood physical or sexual trauma, and indicators of the ‘soft’ side of the bipolar spectrum. Neurophysiologic studies also suggest that chronic, early-onset atypical depressions differ from both melancholia and normality. Re-analyses of the Columbia group's seminal studies suggest that preferential response to phenelzine vs imipramine—arguably the strongest validator of atypical depression—similarly appears to be limited to patients with chronic, early-onset syndromes. The criteria for atypical depression need to be revised in DSM-V, including sharpening the operational definitions for the specific symptoms. The importance of age of onset and comorbid anxiety warrant further study. Research examining the validity of a subform of atypical depression characterized by trait-like interpersonal sensitivity and a chronic, early-onset course may further enhance the clinical utility of the DSM-V classification. [ABSTRACT FROM AUTHOR]

This study investigated whether rasagiline and selegiline (MAO-B inhibitors) induce serotonin syndrome in fluoxetine-treated rats. Rats received rasagiline (0.1, 0.5, 2.0 mg/kg), or selegiline (0.8, 4.0, 16.0 mg/kg) (doses reflecting the clinical ratio of 1:8 base) in drinking water for 28 days. During the last 21 days, they received injections of fluoxetine 10 mg/kg (controls received water only, then saline injections; a fluoxetine only group received water only then fluoxetine). Serotonin syndrome was assessed using neurological severity score (NSS), food intake and weight gain. Mean NSS significantly increased, and weight and food consumption significantly decreased in rats receiving fluoxetine alone compared with controls. Selegiline 16 mg/kg but not rasagiline (regardless of dose) exacerbated these effects. We concluded that selegiline’s amphetamine-like metabolites may increase synaptic cathecholamines and possibly serotonin, aggravating fluoxetine’s effect. Rasagiline is devoid of this effect and may therefore be safer for use with serotonergic drugs in parkinsonian patients. [ABSTRACT FROM AUTHOR]

Although nicotine is generally considered to be the main compound responsible for the addictive properties of tobacco, experimental data indicate that nicotine does not exhibit all the characteristics of other abused substances, such as psychostimulants and opiates. For example, nicotine is only a weak locomotor enhancer in rats and generally fails to induce a locomotor response in mice. This observation contradicts the general consensus that all drugs of abuse release dopamine in the nucleus accumbens, a subcortical structure, and thus increase locomotor activity in rodents. Because tobacco smoke contains monoamine oxidase inhibitors (MAOIs) and decreases MAO activity in smokers, we have combined MAOIs with nicotine to determine whether it is possible to obtain a locomotor response to nicotine in C57Bl6 mice. Among 15 individual or combined MAOIs, including harmane, norharmane, moclobemide, selegiline, pargyline, clorgyline, tranylcypromine and phenelzine, only irreversible inhibitors of both MAO-A and -B (tranylcypromine, phenelzine, and clorgyline+selegiline) allowed a locomotor response to nicotine. The locomotor stimulant interaction of tranylcypromine and nicotine was absent in β2-nicotinic acetylcholine receptor subunit knockout mice. Finally, it was found that, whereas naïve rats did not readily self-administer nicotine (10 μg/kg/injection), a robust self-administration of nicotine occurred when animals were pretreated with tranylcypromine (3 mg/kg). Our data suggest that MAOIs contained in tobacco and tobacco smoke act in synergy with nicotine to enhance its rewarding effects.Neuropsychopharmacology (2006) 31, 1704–1713. doi:10.1038/sj.npp.1300987; published online 14 December 2005 [ABSTRACT FROM AUTHOR]

The purpose of this article is to compare and contrast the benefits and limitations of antidepressant drugs. Several different classes of antidepressants are available for treatment of major depressive disorder, each with its own benefits and limitations as a result of its pharmacological profile. Tricyclic antidepressants (TCAs) and monoamine oxidase (MAO) inhibitors are effective in a large proportion of depressed patients, but their use is often limited by short- and long-term safety/tolerability problems. Selective serotonin reuptake inhibitors (SSRIs) exhibit comparable efficacy to TCAs in most patients, but may be less effective in certain patients. Additionally, SSRI use may by impacted by clinically significant drug interactions. Venlafaxine is a selective serotonin-noradrenaline reuptake inhibitor (SNRI) with unique pharmacological properties that may enhance its efficacy as well as its safety profile. In clinical trials, venlafaxine exhibits antidepressant activity in a broad range of patients with major depression, including those with melancholia, agitated or retarded symptoms, anxiety symptoms, and refractory or resistant depression. Venlafaxine has shown potential for an early onset of action and offers dose flexibility that may allow recruitment of additional responders at higher dosages. Because of its lack of affinity for muscarinic cholinergic, histaminergic, and alpha[sub 1] -adrenergic receptors, venlafaxine has a safety profile that is superior to that of TCAs. Venlafaxine also is devoid of the drug interactions characteristic of SSRIs. © 1997 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Influence of acute and chronic administration of two types of antidepressant drugs i.e. tricyclic compounds and monoamine oxidase inhibitors (MAOIs), on the Open Field behaviour in rats was examined. Two types of stereotyped behaviour were observed in the open field test namely simple stereotypy (ambulation) and complex stereotypy (rearing). Chronic administration of MAOIs primarily caused an increase in the simple stereotyped behaviour while tricyclic compounds on repeated administration selectively increased complex stereotyped behaviour. The Open Field behaviour of rats due to MAOIs is comparable to hallucinogens while the pattern seen with tricyclic agent differs from MAOIs and other central nervous system stimulant drugs. [ABSTRACT FROM AUTHOR]

Abstract: A series of 6-methyl-3-phenylcoumarins 3-6 were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. A comparative study between the three possible mono methoxy 3-phenyl derivatives and the p-hydroxy analogue is reported. The synthesis of these new resveratrol-coumarin hybrids was carried out by a Perkin reaction between the 5-methylsalicylaldehyde and the corresponding phenylacetic acids. The p-methoxy substituted compound 3 was hydrolyzed to 6 by a traditional reaction with hydriodic acid. The prepared compounds show high selectivity to the MAO-B isoenzyme, some of them with IC50 values in the low nanomolar range. Compound 4, with the methoxy group in meta position, is the most active of this series, with an IC50 against MAO-B of 0.80nM, and is several times more potent and MAO-B selective than the R-(−)-deprenyl (reference compound). [Copyright &y& Elsevier]

Extensive studies showed that monoaminergic neurotransmission that involves serotonin (5-HT), norepinephrine (NE) and dopamine (DA) exerts major influence on brain circuits concerned by the regulation of mood, reactivity to psychological stress, self-control, motivation, drive, and cognitive performance. Antidepressants targeting monoamines directly affect the functional tone of these circuits, notably in limbic and frontocortical areas, and evidence has been provided that this action plays a key role in their therapeutic efficacy. Indeed, at least some of functional changes detected by functional magnetic resonance imaging in emotion- and cognitive-related circuits such as the one involving limbic-cortical-striatal-pallidal-thalamic connections in depressed patients can be reversed by monoamine-targeted antidepressants. However, antidepressants acting selectively on only one monoamine, such as selective inhibitors of 5-HT or NE reuptake, alleviate depression symptoms in a limited percentage of patients, and are poorly effective to prevent recurrence. Thorough investigations for the last 30 years allowed the demonstration of the existence of functional interactions between 5-HT, NE and DA systems, and the identification of the specific receptors involved. In particular, 5-HT systems were shown to exert negative influence on NE and DA systems through 5-HT2A and 5-HT2C receptor- mediated mechanisms, respectively. On the other hand, complex positive and negative influences of NE system on 5-HT neurotransmission are mediated through α1- and α2-adrenergic receptors, respectively. These data provided a rationale for the design of new, multimodal, therapeutic strategies involving drugs acting not only at the "historical" targets such as the 5-HT and/or the NE transporter, but also at other molecular targets to improve their efficacy and their tolerability., (Copyright © 2013 Elsevier Inc. All rights reserved.)