5-HT_1A Receptor

Vilazodone has an IC50 of 0.5 nM for the SERT and 0.2 nM at the human 5-HT₁A receptor. Vilazodone exhibits high affinity (pKi≥9.3) for human recombinant and native tissue 5-HT₁A receptors from rats, mice, marmosets, and guinea pigs, and it preferentially binds to the high agonist affinity state of human 5-HT₁A receptors. Vilazodone functions at 5-HT₁A receptors as a partial agonist with high efficacy. A single concentration of Vilazodone (100nM) increases basal binding by approximately 70% of that produced by the full 5-HT₁A receptor agonist, 8‐OH‐PIPAT, in [³⁵S]GTPγS binding studies in Sf9 cells expressing h5-HT₁A receptors. Vilazodone exhibits potent partial agonistic effects on the 5‐HT1A receptor, as demonstrated by [³⁵S]GTPγS binding studies conducted in rat hippocampal membranes. Its intrinsic activity is 0.61 and its pEC50 is 8.1. Vilazodone has a potent inhibitory effect on 5‐HT reuptake in the cortex of rats and guinea pigs. Vilazodone has an 8.8 pIC50 to inhibit [3H]5-HT uptake in LLCPK cells that express human SERT[1].

Vilazodone (intraperitoneal injection; 3 mg/kg ; single dose) causes increases in extracellular 5‐HT in rat frontal cortex (FC) and ventral hippocampal (vHipp) in in vivo microdialysis studies. Maximum increases are seen at 3 mg/kg, where they reach, in the FC and vHipp, 527% and 558% of preinjection baseline values, respectively[2]. Vilazodone (55 mg/kg; single dose; oral gavage) inhibits vocalizations induced by stress in the rat ultrasonic vocalizations test 120 and 210 minutes after the dose[2].

The receptor binding profile of vilazodone was reported by Heinrich et al. Here vilazodone demonstrated an IC50 of 0.2 nM at the human 5‐HT1A receptor and 0.5 nM for the SERT. Its closest cross affinity in these studies was to the dopamine D3 receptor (IC50 of 71 nM) followed by the 5‐HT4 receptor (IC50 of 252 nM). Our own in house radioligand binding studies using the 5‐HT1A receptor agonist [3H]8‐OH‐DPAT have demonstrated that vilazodone displayed high affinity (pKi≥ 9.3) for human recombinant and rat, guinea pig, mouse, and marmoset native tissue 5‐HT1A receptors (unpublished data in Table 1). In contrast, vilazodone displaced the antagonist radioligand, [3H]WAY100635, binding (in the presence of Gpp(NH)p) with pKi values up to 2 log units lower than those obtained using [3H]8‐OH‐DPAT (Table 2). These data suggest that vilazodone preferentially binds to the high agonist affinity state of human 5‐HT1A receptors, indicative of this molecule's partial agonist activity. It has been reported that the difference in affinity of a compound for 5‐HT1A receptors, as measured using [3H]8‐OH‐DPAT versus [3H]WAY100635, is directly proportional to its intrinsic agonist activity. Thus, given that the difference in affinity, as measured against [3H]8‐OH‐DPAT cf. [3H]WAY100635, was similar to that observed with the endogenous agonist 5‐HT, these data suggest that vilazodone would act as a high efficacy partial agonist at 5‐HT1A receptors. This hypothesis was supported in [35S]GTPγS binding studies in Sf9 cells expressing h5‐HT1A receptors, whereby a single concentration of vilazodone (100nM) increased basal binding by approximately 70% of that produced by the full 5‐HT1A receptor agonist, 8‐OH‐PIPAT. However, given that only single concentrations were used in this study, accurate determination of intrinsic activity or functional potency at h5‐HT1A receptors could not be achieved. More extensive studies in HEK cells expressing h5‐HT1A receptors have since been performed (unpublished data). In these studies, vilazodone acted as a full agonist, as compared to 5‐HT, with a pEC50 of 9.0.[1]

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In comparison, the 5-HT1A/B/D receptor partial agonist SB-272183 ((5-Chloro-2, 3-dihydro-6-[4-methylpiperazin-1-yl]-1[4-pyridin-4-yl]napth-1-ylaminocarbonyl]-1H-indole), which has been reported to act as a 5-HT1A receptor antagonist at rodent and human native tissue 5-HT1A receptors, displayed an intrinsic activity of approximately 0.3 in the same study (Fig. 2). Interestingly, in [35S]GTPγS binding studies in rat hippocampal membranes (a functional preparation in which 5-HT1A receptors predominate), vilazodone acted as a potent 5-HT1A receptor partial agonist with a pEC50 of 8.1 and an intrinsic activity of 0.61. In comparison, (±) 8-OH-DPAT (pEC50 7.2) produced a partial agonist response with an intrinsic activity of 0.45 and the partial agonist buspirone showed a pEC50= 6.5 ± 0.35 and an intrinsic activity of 0.19. Taken together, these data suggest that vilazodone would be a high efficacy 5-HT1A receptor partial agonist, in vivo. The apparent difference in intrinsic activities between recombinant and native tissue systems may be a consequence of varying degrees of receptor reserve. Indeed, receptor reserve has been reported to be present for native tissue somatodendritic 5-HT1A autoreceptors in vivo[49] but not native postsynaptic 5-HT1A receptors in vitro, which would explain why vilazodone demonstrated partial agonist properties in the hippocampus. Therefore, one possible conclusion is that vilazodone is a 5-HT1A receptor partial agonist with the potential to act as a full agonist in systems with high receptor reserve and/or improved receptor–G protein coupling efficiency. This concept is supported by the observation that vilazodone appeared to have much higher efficacy at pre- versus postsynaptic 5-HT1A receptors in some in vivo models but is perhaps contradicted by some of the neurochemical observations.[1]

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Combinations of biochemical and electrophysiological studies have demonstrated that vilazodone acts as a potent 5-HT reuptake inhibitor in rat and guinea pig cortex. We have confirmed this high potency in LLCPK cells expressing human SERT, whereby vilazodone inhibited [3H]5-HT uptake with a pIC50 of 8.8 ± 0.05 (Fig. 3). This potency value is approximately 1 log unit greater than that for fluoxetine but similar to that for paroxetine (unpublished observations). These data, taken together with the observation that vilazodone is a potent 5-HT1A receptor partial agonist, puts this molecule in a novel class of compound that has the potential to rapidly desensitize 5-HT1A autoreceptors both directly, via 5-HT1A receptor agonism, and indirectly, via elevations in endogenous 5-HT through SERT inhibition.[1]

Efficacy in Models of Anxiety[1]
Three separate studies have evaluated the efficacy of vilazodone in various rodent models thought to be predictive of anxiolytic activity. In the rat ultrasonic vocalizations test, stress-induced vocalizations were inhibited by vilazodone (55 mg/kg po) at 120 and 210 min post dose. In comparison, 8-OH-DPAT (0.55 mg/kg sc) produced a similar, but shorter duration, activity that was reversed by WAY 100635. In contrast, the SSRI fluoxetine (100 mg/kg po) was without effect unless combined with 8-OH-DPAT. Together these data suggest that the vilazodone-mediated efficacy in this model was via its 5-HT1A receptor agonist activity. In two further rat models of anxiety, that is, the elevated plus maze and the shock-probe burying tests, vilazodone demonstrated dose related efficacy (10–40 mg/kg ip) in the shock probe test but, interestingly, was without effect in the elevated plus maze. The positive control diazepam produced efficacy in both paradigms. Finally, vilazodone was examined in a predator-induced stress paradigm, brought about by unprotected exposure to a domestic cat. Predator stress increased anxiety-like behaviors in the elevated plus maze and an increased response to an acoustic startle. Vilazodone (20–40 mg/kg ip), administered acutely or prophylactically (1 week prior to behavioral testing), attenuated stress-induced potentiated startle but had no effect on stress potentiated anxiety response in the elevated plus maze. Interestingly, a lower dose of 10 mg/kg of vilazodone had the opposite effect in the startle response, indicating a somewhat unexplained bidirectional effect, and all doses produced a potentiation of the startle-induced stress response possibly suggestive of an anxiogenic-like response. Finally, the data from these studies also showed that vilazodone had neither sedation nor stimulatory effects but did produce context-dependent efficacy.

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Efficacy in Models of Antidepressant Activity[1]
The FST is widely used to assess the potential of molecules to exhibit an antidepressant profile since all major classes of antidepressant drugs, including tricyclic antidepressants (TCA), SNRI and SSRI, monoamine oxidase inhibitors, and atypical ADs [70–74], are effective in this stress based model. Page et al.demonstrated that vilazodone produced efficacy (i.e., a reduction in immobility time) in both the rat and mouse versions of this model at a single dose (1 mg/kg ip), whilst higher doses (3 and 10 mg/kg) were without effect. The magnitude of this efficacy was approximately similar to that of fluoxetine. Efficacy in this model is generally considered to be mediated by 5-HT and blocked by receptor antagonists and genetic deletions of 5-HT1A receptors. Thus vilazodone-mediated efficacy may be via direct 5-HT1A receptor agonism or alternatively indirect through elevations in endogenous 5-HT. Perhaps the major driving force behind this mechanistic combination of these two activities is a hastened desensitization of 5-HT1A receptors leading to an enhanced onset of therapeutic activity. Therefore some evaluation of the onset of preclinical efficacy in models thought to mimic this, such as rodent social interaction or schedule induced polydipsia, would be useful but unfortunately has not been reported to date.

Absorption, Distribution and Excretion
Vilazodone's bioavailability is 72% when taken with food.
1% of the dose is recovered unchanged in the urine and 2% of the dose is recovered unchanged in the feces.
Vilazodone's volume of distribution is unknown but large
Clearance of vilazodone is 19.9-25.1L/h in patients with mild to moderate renal impairment compared to 26.4-26.9L/h in healthy controls.
Vilazodone concentrations peak at a median of 4-5 hours (Tmax) after administration and decline with a terminal half-life of approximately 25 hours. The absolute bioavailability of vilazodone is 72% with food. Administration of VIIBRYD with food (high fat or light meal) increases oral bioavailability (Cmax increased by approximately 147-160%, and AUC increased by approximately 64-85%).
Vilazodone is widely distributed and approximately 96-99% protein-bound.
Vilazodone is excreted into the milk of lactating rats.

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Metabolism / Metabolites
Vilazodone is mainly metabolized by cytochrome P450(CYP)3A4 and also to a minor extent by CYP2C19 and CYP 2D6. Although the metabolic pathway for vilazodone has not been fully studied, a proposed mechanism for metabolism in rats was published in 2017.
Viibryd is extensively metabolized through CYP and non-CYP pathways (possibly by carboxylesterase), with only 1% of the dose recovered in the urine and 2% of the dose recovered in the feces as unchanged vilazodone. CYP3A4 is primarily responsible for its metabolism among CYP pathways, with minor contributions from CYP2C19 and CYP2D6. In vitro studies with human microsomes and human hepatocytes indicate that vilazodone is unlikely to inhibit or induce the metabolism of other CYP (except for CYP2C8) substrates; and an in vivo study with probe substrates for CYP2C19, 2D6 and 3A4 showed vilazodone did not alter the pharmacokinetics of the probe substrates. However, an in vivo study with probe substrate for CYP2C19 demonstrated a minor induction of CYP2C19. Strong inhibitors of CYP3A4 (e.g., ketoconazole) can reduce the metabolism of vilazodone in vivo and increase exposure. Conversely, strong inducers of CYP3A4 (e.g., carbamazepine) can decrease vilazodone exposure.

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Biological Half-Life
25 hours. Other studies show a half life of 24±5.2h with a single 40mg dose and 28.9±3.2h with repeated doses.
Vilazodone /has/ a terminal half-life of approximately 25 hours.

Toxicity Summary
IDENTIFICATION AND USE: Vilazodone is a white to off-white solid that is formulated into film-coated tablets. Vilazodone is a combined selective serotonin-reuptake inhibitor and serotonin type 1-A (5-hydroxytryptamine (5-HT1A) receptor partial agonist. It is used for the treatment of major depressive disorder in adults. HUMAN EXPOSURE AND TOXICITY: In clinical trials toxic effects of vilazodone at 200-280 mg included serotonin syndrome, lethargy, restlessness, hallucinations, and disorientation. Serotonin syndrome, a potentially life-threatening toxicity has also been reported at therapeutic doses. Serotonin syndrome symptoms may include mental status changes (agitation, hallucinations, delirium, and coma), autonomic instability (tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (nausea, vomiting, diarrhea). While serotonin syndrome has been reported during vilazodone monotherapy, it is a particular concern when used with other serotonergic drugs and with drugs that impair metabolism of serotonin (in particular, monamine oxidase inhibitors (MAOIs). The concomitant use of vilazdone with MAOIs intended to treat psychiatric disorders is contraindicated. Vilazodone is also not approved for use in pediatric patients. Pooled analyses of short-term placebo-controlled studies of antidepressant drugs (selective serotonin reuptake inhibitors and others) showed that these drugs increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. Also, some neonates exposed to serotonegic antidepressants (including vilazodone) late in the third trimester of pregnancy have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. In some cases, the clinical picture is consistent with serotonin syndrome. Infants exposed to vilazodone in pregnancy may also have an increased risk for persistent pulmonary hypertension of the newborn, a rare heart and lung condition associated with substantial neonatal morbidity and mortality. ANIMAL STUDIES: Vilazodone caused some developmental toxicity in rats, but was not teratogenic in rats or rabbits. When vilazodone was administered to pregnant rats at an oral dose of 30 times the maximum recommended human dose during the period of organogenesis and throughout pregnancy and lactation, the number of live born pups was decreased. There was an increase in early postnatal pup mortality, and among surviving pups there was decreased body weight, delayed maturation, and decreased fertility in adulthood. There was some maternal toxicity at this dose.

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Interactions
Concomitant administration of vilazodone and moderate CYP3A4 inhibitors (e.g., erythromycin) can result in increased plasma vilazodone concentrations. During concurrent administration with moderate inhibitors of CYP3A4 (e.g., erythromycin), the dosage of vilazodone should be reduced to 20 mg once daily in patients experiencing intolerable adverse effects.
Concomitant administration of vilazodone and potent CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) can increase plasma vilazodone concentrations by approximately 50%. The manufacturer states that the dosage of vilazodone should be reduced to 20 mg once daily if administered concomitantly with a potent CYP3A4 inhibitor.
Potentially serious, sometimes fatal adverse reactions may occur in patients who are receiving or have recently received a monoamine oxidase (MAO) inhibitor and then initiate therapy with antidepressant(s) that are pharmacologically similar to vilazodone (e.g., SSRIs), or in those who received SSRI therapy shortly before initiation of an MAO inhibitor. Concomitant use of MAO inhibitors with vilazodone is contraindicated. In addition, at least 2 weeks should elapse between discontinuance of an MAO inhibitor and initiation of vilazodone and vice versa.
Linezolid, an anti-infective agent that is also a reversible MAO inhibitor, has been associated with drug interactions resulting in serotonin syndrome, including some associated with SSRIs. Because of this potential risk, linezolid generally should not be used in patients receiving vilazodone. While the US Food and Drug Administration (FDA) has not received reports of serotonin syndrome with concomitant use of linezolid and vilazodone to date, the risk is considered comparable to that with SSRIs. However, the FDA states that certain life-threatening or urgent situations may necessitate immediate linezolid treatment in a patient receiving a serotonergic drug. In such emergency situations, the availability of alternative anti-infectives should be considered and the benefits of linezolid should be weighed against the risk of serotonin syndrome. If linezolid is indicated in such emergency situations, vilazodone must be immediately discontinued and the patient monitored for symptoms of CNS toxicity for 2 weeks or until 24 hours after the last linezolid dose, whichever comes first. Treatment with vilazodone may be resumed 24 hours after the last linezolid dose. If nonemergency use of linezolid is being planned for a patient receiving vilazodone, vilazodone should be withheld for at least 2 weeks prior to initiating linezolid. Treatment with vilazodone should not be initiated in a patient receiving linezolid; when necessary, vilazodone may be started 24 hours after the last linezolid dose.
For more Interactions (Complete) data for Vilazodone (13 total), please visit the HSDB record page.

[1]. Vilazodone: A 5-HT1A Receptor Agonist/Serotonin Transporter Inhibitor for the Treatment of Affective Disorders CNS Neuroscience & Therapeutics Volume 15, Issue 2, pages 107-117, June 2009

[2]. Vilazodone HCl (Viibryd): A Serotonin Partial Agonist and Reuptake Inhibitor For the Treatment of Major Depressive Disorder. P T. 2012 Jan;37(1):28-31.

Therapeutic Uses
Antidepressant
Viibryd is indicated for the treatment of major depressive disorder (MDD). The efficacy of Viibryd was established in two 8-week, randomized, double-blind, placebo-controlled trials in adult patients with a diagnosis of MDD. Major depressive disorder consists of one or more major depressive episodes. A major depressive episode (DSM-IV-TR) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, or a suicide attempt or suicidal ideation. /Included in US product label/
EXPL THER Sexual dysfunction is common in major depressive disorder (MDD), and many serotonergic antidepressants adversely affect sexual function. Vilazodone, a novel serotonin (5-HT) reuptake inhibitor and 5-HT1A partial agonist approved for MDD, exerts its effects at the 5-HT transporter and at both presynaptic and postsynaptic 5-HT1A receptors. This mechanism may limit sexual dysfunction. AIM: To summarize effects of vilazodone (40 mg/day, with food) on sexual function in adults with MDD, /data was used from/ three Phase III studies: two 8-week, placebo-controlled studies and a 52-week open-label study . Sexual function was assessed by analyzing changes from baseline to end of treatment (EOT) using validated measures. Population included 869 patients (vilazodone, 436; placebo, 433) from placebo-controlled studies and 599 patients from the open-label study. Sexual dysfunction prevalence was high (50%, men; 68%, women) before treatment and declined during treatment in vilazodone and placebo groups, indicating improvement on average. At EOT, stable/improved sexual function was observed in > or = 91% of patients in placebo-controlled studies; treatment group differences in sexual dysfunction at EOT were not statistically significant for either sex. Differences vs. placebo in changes from baseline of sexual function scores were small and were generally not statistically significant; effect sizes (Cohen's D) were generally of low magnitude. In the placebo-controlled studies, 8.0% of vilazodone-treated patients and 0.9% of placebo-treated patients reported > or = 1 sexual-function-related treatment-emergent adverse event (P<0.001). Half of men and two thirds of women with MDD had sexual dysfunction at baseline; sexual function improved on average in both vilazodone and placebo groups. Results suggest that vilazodone may have a small adverse impact on sexual function in adults with MDD relative to the high prevalence of sexual dysfunction at baseline.

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Drug Warnings
/BOXED WARNING/ WARNING: SUICIDAL THOUGHTS AND BEHAVIORS. Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for clinical worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. Viibryd is not approved for use in pediatric patients.
Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric patients with major depressive disorder or other psychiatric disorders, whether or not they are taking antidepressants. This risk may persist until clinically important remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. However, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term, placebo-controlled studies of antidepressants (i.e., selective serotonin-reuptake inhibitors (SSRIs) and other antidepressants) have shown an increased risk of suicidality in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders. An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults older than 24 years of age, and a reduced risk was observed in adults 65 years of age or older. The US Food and Drug Administration (FDA) recommends that all patients being treated with antidepressants for any indication be appropriately monitored and closely observed for clinical worsening, suicidality, and unusual changes in behavior, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, also should be advised to monitor patients on a daily basis for the emergence of agitation, irritability, or unusual changes in behavior as well as the emergence of suicidality, and to report such symptoms immediately to a health-care provider. Although a causal relationship between the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consequently, consideration should be given to changing the therapeutic regimen or discontinuing therapy in patients whose depression is persistently worse or in patients experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if such manifestations are severe, abrupt in onset, or were not part of the patient's presenting symptoms. If a decision is made to discontinue therapy, vilazodone dosage should be tapered as rapidly as is feasible but consideration should be given to the risks of abrupt discontinuance. FDA also recommends that the drugs be prescribed in the smallest quantity consistent with good patient management, in order to reduce the risk of overdosage.
Potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with antidepressants alone, but particularly with concurrent use of other serotonergic drugs (including serotonin (5-hydroxytryptamine; 5-HT) type 1 receptor agonists (triptans)), drugs that impair the metabolism of serotonin (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists. Manifestations of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea). In its most severe form, serotonin syndrome may resemble NMS, which is characterized by hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation in vital signs, and mental status changes. Patients receiving vilazodone should be monitored for the development of serotonin syndrome or NMS-like signs and symptoms. Concurrent or recent (i.e., within 2 weeks) therapy with MAO inhibitors intended to treat depression is contraindicated. If concurrent therapy with vilazodone and a 5-HT1 receptor agonist (triptan) is clinically warranted, the patient should be observed carefully, particularly during initiation of therapy, when dosage is increased, or when another serotonergic agent is initiated. Concomitant use of vilazodone and serotonin precursors (e.g., tryptophan) is not recommended. If signs and symptoms of serotonin syndrome or NMS occur, treatment with vilazodone and any concurrently administered serotonergic or antidopaminergic agents, including antipsychotic agents, should be immediately discontinued and supportive and symptomatic treatment initiated.
Infants exposed to selective serotonin-reuptake inhibitors (SSRIs) in pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). PPHN occurs in 1-2 per 1,000 live births in the general population and is associated with substantial neonatal morbidity and mortality. Several recent epidemiologic studies suggest a positive statistical association between SSRI use (including Viibryd) in pregnancy and PPHN. Other studies do not show a significant statistical association.
For more Drug Warnings (Complete) data for Vilazodone (16 total), please visit the HSDB record page.

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Pharmacodynamics
Vilazodone increases serotonin levels in the brain by inhibiting the reuptake of serotonin while acting as a partial agonist on serotonin-1A receptors. Due to this activity vilazodone has sometimes been referred to as a selective partial agonist and reuptake inhibitor (SPARI).

C₂₆H₂₇N₅O₂

441.52

441.22

163521-12-8

Vilazodone Hydrochloride; 163521-08-2; Vilazodone-d8; 1794789-93-7; Vilazodone carboxylic acid; 163521-19-5

6918314

White to light yellow solid powder

1.34 g/cm3

745.1ºC at 760 mmHg

203-205ºC

5.534

2

5

7

33

729

0

SGEGOXDYSFKCPT-UHFFFAOYSA-N

InChI=1S/C26H27N5O2/c27-16-18-4-6-23-22(13-18)19(17-29-23)3-1-2-8-30-9-11-31(12-10-30)21-5-7-24-20(14-21)15-25(33-24)26(28)32/h4-7,13-15,17,29H,1-3,8-12H2,(H2,28,32)

5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carboxamide

EMD 68843; SB659746A; 5-(4-(4-(5-Cyano-1H-indol-3-yl)butyl)piperazin-1-yl)benzofuran-2-carboxamide; Viibryd; EMD 515259; vilazodona; vilazodonum; UNII-S239O2OOV3; Vilazodone; EMD68843; EMD-68843

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 75~88 mg/mL (199.3~169.9 mM)
Ethanol: ~14 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)