Pharmacological studies on YM992, a novel antidepressant with selective serotonin re-uptake inhibitory and 5-HT2A receptor antagonistic activity

Takeuchi, Hiromi; Yatsugi, Shin-ichi; Hatanaka, Ken-ichi; Nakato, Kazuhiro; Hattori, H.; Sonoda, Rie; Koshiya, Kazuo; Fujii, Mitsuo; Yamaguchi, Tokio

doi:10.1016/s0014-2999(97)10108-x

Cited by 36 publications

(24 citation statements)

References 18 publications

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“…Fluoxetine had no significant effect in this study; however, several reports have indicated the lack of efficacy of SSRIs compared to TCAs in the TST (8).…”

contrasting

confidence: 78%

Comparison of Noradrenergic and Serotonergic Antidepressants in Reducing Immobility Time in the Tail Suspension Test

Fujishiro

Imanishi

Baba

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-We examined the effects of two noradrenergic tricyclic antidepressants and two selective serotonin re-uptake inhibitors in the tail suspension test, with a suspension period of 30 min instead of the usual 10 min. Within the first 10 min, desipramine, nortriptyline and fluvoxamine significantly reduced the duration of immobility. Whereas desipramine and nortriptyline were also efficacious in the rest of the test period, fluvoxamine was not. Fluoxetine showed no significant effect throughout the study period. These results suggest that a prolonged tail suspension test results in functional changes in the noradrenergic and serotonergic systems and alters the sensitivity to antidepressants.

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“…Fluoxetine had no significant effect in this study; however, several reports have indicated the lack of efficacy of SSRIs compared to TCAs in the TST (8).…”

contrasting

confidence: 78%

Comparison of Noradrenergic and Serotonergic Antidepressants in Reducing Immobility Time in the Tail Suspension Test

Fujishiro

Imanishi

Baba

et al. 2001

Japanese Journal of Pharmacology

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“…Their order of potency was correlated with their 5-HT re-uptake inhibition activities in the l-5-HTP potentiation study (5). YM992 exhibits 5-HT re-uptake inhibition and 5-HT 2A -receptor antagonistic activity (4,5). This property would contribute to efficacy of YM992 in various tests for evaluating antidepressant activity (5).…”

mentioning

confidence: 99%

“…YM992 ((S)-2-[[(7-fluoroindan-4-yl)oxy]methyl]morpholine) monohydrochloride is a novel compound with selective 5-HT reuptake inhibition and 5-HT2A receptor antagonistic activity (4). The pharmacological profile of YM992 is different from that of TCAs and SSRIs, and it shows high efficacy in various tests, some of which predict the antidepressant activity of drugs (5).…”

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confidence: 99%

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Effect of YM992, a Novel Antidepressant With Selective Serotonin Re-uptake Inhibitory and 5-HT2A Receptor Antagonistic Activity, on a Marble-Burying Behavior Test as an Obsessive-Compulsive Disorder Model

Takeuchi¹,

Yatsugi²,

Yamaguchi³

2002

Japanese Journal of Pharmacology

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ABSTRACT-YM992 ((S)-2-[[ (7-fluoroindan-4-yl)oxy]methyl]morpholine) monohydrochloride is a novel antidepressant with selective serotonin (5-hydroxytryptamine, 5-HT) re-uptake inhibition and 5-HT 2A receptor antagonistic activity. The effects of YM992 and two selective 5-HT re-uptake inhibitors (SSRIs) were studied in a marble-burying behavior test as a model of an obsessive-compulsive disorder (OCD) in mice at doses of 5, 10 and 15 mg /kg, i.p. YM992 and fluoxetine significantly inhibited marble-burying behavior at a dose of 15 mg /kg (i.p.) without affecting spontaneous locomotor activities. Citalopram also significantly inhibited the behavior at doses of 5, 10 and 15 mg /kg (i.p.) without affecting spontaneous locomotor activities. These results suggest that YM992, as well as SSRIs, may exhibit anti-OCD activity in addition to an antidepressive effect in clinical use.

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“…Another compound YM 35992 (Fig. 4), which exhibit 5-HT 2A receptor blocking properties together with more potent reuptake inhibition, may prove to be more promising [101,102].…”

Section: Drugs Targeting Serotonin Receptorsmentioning

confidence: 99%

Trends in the Development of New Antidepressants. Is there a Light at the End of the Tunnel?

Pacher¹,

Kecskeméti²

2004

CMC

167

104

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Since the introduction of tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) in mid-1950's, treatment of depression has been dominated by monoamine hypotheses. The well-established clinical efficacy of TCAs and MAOIs is due, at least in part, to the enhancement of noradrenergic or serotonergic mechanisms, or to both. Unfortunately, their very broad mechanisms of action also include many unwanted effects related to their potent activity on cholinergic, adrenergic and histaminergic receptors.The introduction of selective serotonin reuptake inhibitors (SSRIs) over twenty years ago had been the next major step in the evolution of antidepressants to develop drugs as effective as the TCAs but of higher safety and tolerability profile. During the past two decades SSRIs (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram) gained incredible popularity and have become the most widely prescribed medication in the psychiatric practice. The evolution of antidepressants continued resulting in introduction of selective and reversible monoamine oxidase inhibitors (eg. moclobemid), selective noradrenaline (eg. reboxetine), dual noradrenaline and serotonin reuptake inhibitors (milnacipram, venlafaxin, duloxetin) and drugs with distinct neurochemical profiles such as mirtazapine, nefazadone and tianeptine. Different novel serotonin receptor ligands have also been intensively investigated. In spite of the remarkable structural diversity, most currently introduced antidepressants are 'monoamine based'. Furthermore, these newer agents are neither more efficacious nor rapid acting than their predecessors and approximately 30% of the population do not respond to current therapies.By the turn of the new millennium, we are all witnessing a result of innovative developmental strategies based on the better understanding of pathophysiology of depressive disorder. Several truly novel concepts have emerged suggesting that the modulation of neuropeptide (substance P, corticotrophin-releasing factor, neuropeptide Y, vasopressin V 1b , melanin-concentrating hormone-1), N-methyl-D-aspartate, nicotinic acetylcholine, dopaminergic, glucocorticoid, δ-opioid, cannabinoid and cytokine receptors, gamma-amino butyric acid (GABA) and intracellular messenger systems, transcription, neuroprotective and neurogenic factors, may provide an entirely new set of potential therapeutic targets, giving hope that further major advances might be anticipated in the treatment of depressive disorder soon.The goal of this review is to give a brief overview of the major advances from monoamine-based treatment strategies, and particularly focus on the new emerging approaches in the treatment of depression.

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Pharmacological studies on YM992, a novel antidepressant with selective serotonin re-uptake inhibitory and 5-HT2A receptor antagonistic activity

Cited by 36 publications

References 18 publications

Comparison of Noradrenergic and Serotonergic Antidepressants in Reducing Immobility Time in the Tail Suspension Test

Comparison of Noradrenergic and Serotonergic Antidepressants in Reducing Immobility Time in the Tail Suspension Test

Effect of YM992, a Novel Antidepressant With Selective Serotonin Re-uptake Inhibitory and 5-HT2A Receptor Antagonistic Activity, on a Marble-Burying Behavior Test as an Obsessive-Compulsive Disorder Model

Trends in the Development of New Antidepressants. Is there a Light at the End of the Tunnel?

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