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Purity: ≥98%
Vilazodone HCl (SB659746A; SB659746-A; EMD-68843; EMD68843; Viibryd), the hydrochloride salt of Vilazodone, is a selective serotonin reuptake inhibitor (SSRI) and a partial agonist of 5-HT1A receptors with anti-depressive effects. Vilazodone was given FDA approval in 2011 to treat major depressive disorders. Vilazodone's half-life at the human 5-HT1A receptor is 0.2 nM, while its half-life for the SERT is 0.5 nM. Vilazodone binds to native tissue 5-HT1A receptors in rats, mice, marmosets, and guinea pigs with high affinity (pKi ≥ 9.3), as well as human recombinant receptors.
| Targets |
sPLA2; 5-HT1A Receptor
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
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high affinity (pKi≥ 9.3) for human recombinant and rat, guinea pig, mouse, and marmoset native tissue 5‐HT1A receptors (unpublished data in Table 1).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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| Cell Assay |
Administration of 5-HT1A receptor agonists results in a distinct behavioral syndrome that includes head weaving, tremors, forepaw treading, posture abnormalities, hind limb reduction, and straub tail. At 120 and 210 minutes after dosing, Vilazodone (55 mg/kg po) inhibits stress-induced vocalizations in the rat ultrasonic vocalization exercise. Vilazodone (20–40 mg/kg ip) inhibited stress-induced potentiated startle but had no effect on stress-potentiated anxiety response in the elevated plus maze when given acutely or preventatively one week before behavioral testing. The startle response is interestingly affected in the opposite way by a lower dose of 10 mg/kg of vilazodone, suggesting a bidirectional effect that is not fully understood. Additionally, all doses of the drug increase the startle-induced stress response, which may be indicative of an anxiogenic-like reaction. Vilazodone is an additional treatment option for Major Depressive Disorder.
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| ADME/Pharmacokinetics |
Absorption
Vilazodone's bioavailability is 72% when taken with food. Route of Elimination 1% of the dose is recovered unchanged in the urine and 2% of the dose is recovered unchanged in the feces. Volume of Distribution Vilazodone's volume of distribution is unknown but large Clearance 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%). View More
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. NIH; DailyMed. Current Medication Information for Viibryd (Vilazodone Hydrochloride) Tablet Viibryd (Vilazodone Hydrochloride) Kit (Revised: July 2014). Available from, as of July 30, 2014: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=4c55ccfb-c4cf-11df-851a-0800200c9a66 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. Vilazodone’s pharmacokinetic activity (5–80 mg) is dose-proportional. The terminal half-life is approximately 25 hours. When vilazodone is taken with food, the drug’s absolute bioavailability is 72%. After daily dosing of vilazodone 40 mg under fed conditions, the mean maximum plasma concentration (Cmax) at steady state was 156 ng/mL, and the mean area-under-the-curve (AUC0–24 hr) concentration was 1,645 ng • hours/mL. When vilazodone was administered with a high-fat or light meal, the Cmax was increased by approximately 147% to 160%, and the AUC concentration was increased by approximately 64% to 85%. If vomiting occurs within 7 hours after administration, the drug’s absorption is decreased by about 25%; however, a replacement dose is not required. Vilazodone has a large volume of distribution (value unknown). It is approximately 96% to 99% protein-bound The drug is extensively metabolized in the liver, primarily via the cytochrome P450 (CYP) 3A4 isoenzyme. CYP2C19 and CYP2D6 are minor metabolic pathways. Non-CYP450 metabolism also occurs, possibly by carboxylesterase. Only 1% and 2% of the dose are recovered in urine and feces, respectively, as unchanged vilazodone. The presence of mild or moderate renal and hepatic impairment does not affect the clearance of vilazodone. |
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| Toxicity/Toxicokinetics |
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. Hepatotoxicity In premarketing studies, liver test abnormalities were uncommon in patients taking vilazodone (Likelihood score: E* (unproven but suspected rare cause of clinically apparent liver injury). View More
Effects During Pregnancy and Lactation 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. Antidote and Emergency Treatment /SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/ Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160 /SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/ Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160 /SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/ Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160-1 No specific antidotes for vilazodone are known. In case of an overdose, provide supportive care, including close medical supervision and monitoring. Treatment should consist of those general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdose. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. ... Removal of vilazodone by dialysis has not been studied; however, the high volume of distribution of vilazodone suggests that dialysis will not be effective in reducing vilazodone plasma concentrations. NIH; DailyMed. Current Medication Information for Viibryd (Vilazodone Hydrochloride) Tablet Viibryd (Vilazodone Hydrochloride) Kit (Revised: July 2014). Available from, as of July 30, 2014: https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=4c55ccfb-c4cf-11df-851a-0800200c9a66 Populations at Special Risk Vilazodone has not been systematically evaluated in patients with seizure disorders; such patients were excluded from clinical studies. As with other antidepressants, vilazodone should be used with caution in patients with a history of seizure disorder American Society of Health-System Pharmacists 2014; Drug Information 2014. Bethesda, MD. 2014, p. 2455 Protein Binding: 96-99%. |
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| References | |||
| Additional Infomation |
Vilazodone hydrochloride is a hydrochloride obtained by reaction of vilazodone with one equivalent of hydrochloric acid. Used for the treatment of major depressive disorder. It has a role as an antidepressant, a serotonin uptake inhibitor and a serotonergic agonist. It contains a vilazodone(1+).
A benzofuran, indole, and piperazine derivative that functions as a SEROTONIN UPTAKE INHIBITOR and partial SEROTONIN 5-HT1 RECEPTOR AGONIST. It is used as an ANTIDEPRESSIVE AGENT. See also: Vilazodone (has active moiety). |
| Molecular Formula |
C26H28CLN5O2
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| Molecular Weight |
477.99
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| Exact Mass |
477.193
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| Elemental Analysis |
C, 65.33; H, 5.90; Cl, 7.42; N, 14.65; O, 6.69
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| CAS # |
163521-08-2
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| Related CAS # |
Vilazodone-d8; 1794789-93-7; Vilazodone; 163521-12-8; Vilazodone carboxylic acid; 163521-19-5
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| PubChem CID |
6918313
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| Appearance |
White to yellow solid powder
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| Boiling Point |
745.1ºC at 760 mmHg
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| Melting Point |
279°C(lit.)
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| Flash Point |
404.4ºC
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| LogP |
5.718
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
729
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].O1C(C(N([H])[H])=O)=C([H])C2=C1C([H])=C([H])C(=C2[H])N1C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])C([H])([H])C([H])([H])C2=C([H])N([H])C3C([H])=C([H])C(C#N)=C([H])C2=3)C([H])([H])C1([H])[H]
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| InChi Key |
RPZBRGFNBNQSOP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H27N5O2.ClH/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);1H
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| Chemical Name |
5-[4-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-yl]-1-benzofuran-2-carboxamide;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.23 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0921 mL | 10.4605 mL | 20.9209 mL | |
| 5 mM | 0.4184 mL | 2.0921 mL | 4.1842 mL | |
| 10 mM | 0.2092 mL | 1.0460 mL | 2.0921 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05948579 | Not yet recruiting | Drug: Intervention B Vilazodone Hydrochloride (HCl) Drug: Intervention B Placebo |
Post Traumatic Stress Disorder | U.S. Army Medical Research and Development Command |
August 2023 | Phase 2 |
| NCT05422612 | Recruiting | Drug: Intervention A Placebo Drug: Intervention B Placebo |
Post Traumatic Stress Disorder | U.S. Army Medical Research and Development Command |
November 2, 2023 | Phase 2 |
| NCT02015546 | Completed | Drug: Vilazodone | Major Depressive Disorder (MDD) |
Duke University | December 2012 | Phase 3 |
| NCT02436239 | Completed | Drug: Vilazodone | Major Depressive Disorder | Forest Laboratories | May 2, 2015 | Phase 3 |
| NCT01828515 | Completed | Drug: Vilazodone Drug: Placebo |
Memory Impairment | University of Texas Southwestern Medical Center |
December 2012 | Phase 2 |
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