| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
5-HT2 receptors
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|---|---|
| ln Vitro |
AAZ-A-154 (100 nM) promotes dendritic outgrowth in cultured rat embryonic cortical neurons, increasing dendritic arbor complexity to a comparable extent as ketamine. This psychoplastogenic effect is abolished by the 5-HT2R antagonist ketanserin (1 μM), suggesting that AAZ-A-154 triggers dendritic growth through activation of 5-HT2Rs. [1]
AAZ-A-154 exhibits high selectivity for 5-HT2 receptors as demonstrated using a panel of GPCR-based sensors (dopamine, adrenergic, opioid, and serotonin receptors) in both agonist and antagonist modes. [1]
Schild regression analysis reveals that AAZ-A-154 is a psychLight competitive antagonist. [1]
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| ln Vivo |
AAZ-A-154 (20 mg/kg, i.p.) produces rapid (30 min) and long-lasting (1 week) antidepressant-like effects in the forced swim test (FST) in C57BL/6J mice. The compound decreased immobility in the FST, an effortful behavioral response commonly produced by other known psychoplastogens and antidepressants such as ketamine. [1]
In VMAT2 heterozygous (VMAT2-HET) mice (a model of depression), a single administration of AAZ-A-154 (15 mg/kg, i.p.) produced an anti-anhedonic effect, with treated VMAT2-HET mice exhibiting a sucrose preference indistinguishable from wild-type controls. This effect persisted for at least 12 days. The change in sucrose preference cannot be attributed to differential fluid consumption since both genotypes drank similar volumes of liquids across the entire experiment, and AAZ-A-154 did not modify sucrose preference in wild-type animals. [1]
AAZ-A-154 failed to produce any head-twitch responses (HTR), even at doses as high as 100 mg/kg (i.p.), confirming its non-hallucinogenic nature. However, a high dose of 100 mg/kg decreased locomotion in mice. [1]
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| Enzyme Assay |
While a specific step-by-step protocol was not detailed in the summaries, the standard methodology for characterizing zalsupindole involves radioligand binding assays using membranes from cells expressing human recombinant serotonin receptors (e.g., 5-HT2A, 5-HT2B, 5-HT2C). In these cell-free systems, increasing concentrations of zalsupindole compete with a high-affinity radioligand (such as [3H]-ketanserin for 5-HT2A) to determine its binding affinity (Ki value). Functional bias is subsequently assessed using non-radioactive methods like IP-1 accumulation or β-arrestin recruitment assays to differentiate between Gq and β-arrestin signaling pathways.
|
| Cell Assay |
Dendritogenesis assay in cultured cortical neurons: Timed-pregnant Sprague Dawley rats (E18) were used to obtain cortical neurons. Cultured neurons were treated with AAZ-A-154 (100 nM) or ketamine (1 μM, positive control). To assess the role of 5-HT2Rs, neurons were co-treated with the 5-HT2R antagonist ketanserin (1 μM). After treatment, neurons were fixed and stained, and dendritic arbor complexity was analyzed using Sholl analysis to determine the maximal number of crossings (Nmax). AAZ-A-154 increased Nmax comparable to ketamine, and this effect was blocked by ketanserin. [1]
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| Animal Protocol |
Forced Swim Test (FST) in C57BL/6J mice: Male and female C57BL/6J mice (9-10 weeks old, n=6 per sex per condition) were handled for 3 consecutive days prior to the first FST. Drug-naive mice underwent a pretest swim to induce a depressive-like phenotype. The next day, animals received intraperitoneal injections of AAZ-A-154 (20 mg/kg), ketamine (3 mg/kg, positive control), or vehicle (saline). After 30 minutes, mice underwent a 6-minute swim session in a clear Plexiglas cylinder filled with 30 cm of 24±1°C water. Immobility time (passive floating or remaining motionless with no activity other than keeping the head above water) was scored for the last 4 minutes of the 6-minute trial. One week later, the FST was repeated to assess sustained effects. All FSTs were performed between 0800 and 1300 h. [1]
Head-Twitch Response (HTR) and Locomotion Assays: Both male and female C57BL/6J mice (approximately 8 weeks old, 2 male and 2 female = 4 total per treatment) were used. Compounds were administered intraperitoneally (5 mL/kg) using 0.9% saline as vehicle. After injection, animals were placed into an empty cage, and HTRs were videotaped and scored later by two blinded observers. Locomotion was assessed using automated tracking software. AAZ-A-154 was tested at multiple doses (10, 30, 100 mg/kg) and failed to produce HTRs at any dose, though the 100 mg/kg dose decreased locomotion. [1]
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| ADME/Pharmacokinetics |
In rat studies, zalsupindole demonstrates rapid brain penetration after systemic administration, suggesting good blood-brain barrier permeability. Data from Phase 1 human clinical trials indicate that the drug exhibits linear pharmacokinetics with dose-proportional absorption across a wide range (2 mg to 360 mg). It shows high central nervous system (CNS) penetration, and its absorption profile supports oral dosing. Electroencephalogram (EEG) biomarkers in humans showed dose-dependent increases in power spectra associated with synaptic potentiation, confirming target engagement in the brain.
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| Toxicity/Toxicokinetics |
Preclinical safety assessments highlight a favorable safety profile. Zalsupindole lacks measurable agonism at the 5-HT2B receptor, mitigating the risk of drug-induced valvular heart disease associated with some serotonergic drugs. In Phase 1 clinical trials, oral zalsupindole was reported to be well-tolerated across a dose range of 2–360 mg. There were no reports of psychotomimetic effects (hallucinations or dissociation), traditional drug-related adverse events of psychedelics, or significant toxicity signals.
|
| References |
| Molecular Formula |
C14H21BRN2O
|
|---|---|
| Molecular Weight |
313.23
|
| CAS # |
2930845-96-6
|
| Related CAS # |
2481740-94-5; 2930845-96-6 (HBr); 2930845-92-2 (benzoate); 2930845-89-7 (HCl); 2481740-95-6 (fumarate); 2930845-94-4; 2930846-03-8 (mesylate); 2481741-75-5 (S-isomer free base)
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| Appearance |
Typically exists as solids at room temperature
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| Synonyms |
Zalsupindole HBr; AAZ-A-154 HBr; AAZA154; AAZ-A-154 HBr; AAZA-154 HBr; AAZ-A 154 HBr; AAZ-A154; AAZA 154; DLX-001 HBr; DLX 001 HBr; DLX001 HBr
|
| 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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1925 mL | 15.9627 mL | 31.9254 mL | |
| 5 mM | 0.6385 mL | 3.1925 mL | 6.3851 mL | |
| 10 mM | 0.3193 mL | 1.5963 mL | 3.1925 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.
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