Vilazodone Hydrochloride, a Combined SSRI and 5-HT1A Receptor Agonist for Major Depressive Disordersts

Guay, David R.P.

doi:10.4140/tcp.n.2012.857

Cited by 11 publications

(9 citation statements)

References 19 publications

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“…However, Vilazodon does not display any advantage over existing post-tricyclic antidepressant [54]. In the present study, YL-0919 and fluoxetine behave similar in the behavioral despair paradigms and rat stress model.…”

Section: Discussionmentioning

confidence: 39%

Antidepressant-Like Activity of YL-0919: A Novel Combined Selective Serotonin Reuptake Inhibitor and 5-HT1A Receptor Agonist

Chen¹,

Jin

Zhang³

et al. 2013

PLoS ONE

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It has been suggested that drugs combining activities of selective serotonin reuptake inhibitor and 5-HT1A receptor agonist may form a novel strategy for higher therapeutic efficacy of antidepressant. The present study aimed to examine the pharmacology of YL-0919, a novel synthetic compound with combined high affinity and selectivity for serotonin transporter and 5-HT1A receptors. We performed in vitro binding and function assays and in vivo behavioral tests to assess the pharmacological properties and antidepressant-like efficacy of YL-0919. YL-0919 displayed high affinity in vitro to both 5-HT1A receptor and 5-HT transporter prepared from rat cortical tissue. It exerted an inhibitory effect on forskolin-stimulated cAMP formation and potently inhibited 5-HT uptake in both rat cortical synaptosomes and recombinant cells. After acute p.o. administration, very low doses of YL-0919 reduced the immobility time in tail suspension test and forced swimming test in mice and rats, with no significant effect on locomotor activity in open field test. Furthermore, WAY-100635 (a selective 5-HT1A receptor antagonist, 0.3 mg/kg) significantly blocked the effect of YL-0919 in tail suspension test and forced swimming test. In addition, chronic YL-0919 treatment significantly reversed the depressive-like behaviors in chronically stressed rats. These findings suggest that YL-0919, a novel structure compound, exerts dual effect on the serotonergic system, as both 5-HT1A receptor agonist and 5-HT uptake blocker, showing remarkable antidepressant effects in animal models. Therefore, YL-0919 may be used as a new option for the treatment of major depressive disorder.

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Section: Discussionmentioning

confidence: 39%

Antidepressant-Like Activity of YL-0919: A Novel Combined Selective Serotonin Reuptake Inhibitor and 5-HT1A Receptor Agonist

Chen¹,

Jin

Zhang³

et al. 2013

PLoS ONE

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“…[25,30] The gastrointestinal adverse effects occur mostly in the first week of treatment. Decreased libido, abnormal orgasms, delayed ejaculation, and erectile dysfunction have been experienced by the patients due to vilazodone consumption, [24,25] which occurred in the first month of treatment and did not increase appreciably after that. [32] Levomilnacipran extended release Levomilnacipran extended release (ER) (1S, 2R-milnacipran, F2695) is a FDA approved drug, enantiomer of milnacipran, for the treatment of MDD.…”

Section: Contraindicationsmentioning

confidence: 92%

“…[24,27,30] C max is increased by approximately 147-160% and area under the curve (AUC) is increased by approximately 64-85%. [24,30] It is extensively metabolized primarily by hepatic CYP450 3A4 enzyme system, with a minor pathway of CYP2D6. Also, non-CYP mediated metabolism is involved such as carboxylase.…”

Section: Contraindicationsmentioning

confidence: 97%

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Novel drugs in depression - A new hope

Urade

Mahakalkar

Dakhale

et al. 2015

Int J Nutr Pharmacol Neurol Dis

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According to the World Health Organization (WHO), depression is defined as a common mental disorder with symptoms of depressed mood, loss of interest or pleasure, decreased energy, feelings of guilt or low self-worth, decreased sleep or appetite, and poor concentration. Beginning with the discovery of monoamine oxidase inhibitors (MOAIs), tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are also developed as therapeutic measures for depression. However, management of depression is still challenging to clinicians as many adverse effects are found with these agents and some questions are still unanswered, creating a few lacunae to research. So to fulfill those lacunae, drugs, namely agomelatine, vortioxetine, vilazodone, and levomilnacipran extended release (ER) having different mechanisms have been recently approved by the United States Food and Drug Administration (FDA). Agomelatine helps in the normalization of disturbed circadian rhythm by melatonergic agonist action. Vortioxetine is a serotonin transporter (SERT) blocker with additional actions such as 5HT 3 and 5HT 7 receptors blockade. It is also an agonist of 5HT 1A and a partial agonist of 5HT 1B receptors. It is the first drug in the antidepressant class approved by FDA which has such multimodal actions. Vilazodone is approved by FDA considering its early onset of antidepressant actions. Levomilnacipran ER is an enantiomer of milnacipran, approved recently by FDA for the treatment of major depressive disorder (MDD). This review helps the clinician to choose better drugs according to patient's clinical needs. Significant efforts must be taken for conducting clinical trials assessing the efficacy of combination of drugs having different mechanisms such as agomelatine and vilazodone.

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“…Vilazodone is both a SSRI and a partial agonist at 5HT1A receptors (Guay, 2012). It has almost no affinity to other serotonin receptors.…”

Section: Vilazodonementioning

confidence: 99%

The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants

et al. 2016

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The monoamine hypothesis of depression posits that an imbalance in monoaminergic neurotransmission is causally related to the clinical features of depression. Antidepressants influencing serotonin mainly aim at raising serotonin concentrations, thereby increasing serotonergic transmission at the level of the synapse, for example by inhibiting the serotonin transporter. However, the serotonin system is multifaceted. Different serotonin receptor subtypes turn the serotonergic system into a complex neurochemical arrangement that influences diverse neurotransmitters in various brain regions. Classical antidepressants as well as other psychopharmacological agents have various crucial effects on serotonin receptors. We aim at providing a clinically useful characterization of serotonin receptor subtypes in the treatment of depression. Clarifying the mode of action and the interplay of serotonin receptors with pharmacological agents should help antidepressant mechanisms and typical side effects to be better understood. Against this background, we feature the novel antidepressants vortioxetine, vilazodone and milnacipran/levomilnacipran with regard to their serotonin receptor targets such as the 5-HT1A, 5-HT3 and 5-HT7 which may account for their specific effects on certain symptoms of depression (e.g. cognition and anxiety) as well as a characteristic side-effect profile.

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Vilazodone Hydrochloride, a Combined SSRI and 5-HT1A Receptor Agonist for Major Depressive Disordersts

Cited by 11 publications

References 19 publications

Antidepressant-Like Activity of YL-0919: A Novel Combined Selective Serotonin Reuptake Inhibitor and 5-HT1A Receptor Agonist

Antidepressant-Like Activity of YL-0919: A Novel Combined Selective Serotonin Reuptake Inhibitor and 5-HT1A Receptor Agonist

Novel drugs in depression - A new hope

The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants

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