| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 6 nM (sigma receptor)[1]
sigma-1 (σ1) and sigma-2 (σ2) receptors. Panamesine is a high-affinity sigma receptor antagonist with functional antidopaminergic activity without extrapyramidal side effects, making it a candidate atypical antipsychotic. |
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| ln Vitro |
Panamesine exhibits high affinity for sigma receptor binding sites with an IC50 of 6 nM in radioligand binding assays. It has high selectivity for sigma binding sites. Preclinical studies demonstrate that panamesine has functional antidopaminergic activity without extrapyramidal side effects and a c-fos expression pattern similar to that of atypical neuroleptics.
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| ln Vivo |
A dose-dependent increase in c-fos expression is induced by panamesine (EMD 57445; 0.3, 1, 3, 30 mg/kg) in multiple cortical locations, with the piriform cortex exhibiting the greatest signals[1].
In animal studies, panamesine demonstrated antipsychotic effects and was free of side effects related to the extrapyramidal motoric system (EPMS). In open clinical trials in patients with acute schizophrenia, panamesine showed antipsychotic activity. However, development was discontinued, likely due to insufficient efficacy or tolerability in larger controlled trials. |
| Enzyme Assay |
Cell-free sigma receptor binding assays: Guinea pig brain membranes (sigma-1) or rat liver membranes (sigma-2) are incubated with [3H]-pentazocine (sigma-1, 1-5 nM) or [3H]-DTG (sigma-2, 2-10 nM) in the presence of (+)pentazocine to mask sigma-1 sites for sigma-2 assays. Panamesine is added at increasing concentrations (0.01-1000 nM). Incubation is performed in 50 mM Tris-HCl, pH 8.0, for 120 min at 25degC. Bound radioactivity is separated by GF/B filtration. IC50 is calculated by nonlinear regression. Reported IC50 = 6 nM.
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| Cell Assay |
Cell-based functional assays for sigma receptor antagonism are performed using human sigma receptor-expressing cell lines. Panamesine (0.1-1000 nM) is pre-incubated with cells for 10-15 min, then a sigma agonist (e.g., DTG or PRE-084) is added. Functional readouts include changes in intracellular calcium, cAMP levels, or cell proliferation. The functional antagonistic nature of panamesine has been confirmed by blocking both DTG and rimcazole responses, indicating its functional antagonistic activity at sigma receptors.
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| Animal Protocol |
Animal/Disease Models: Female Sprague Dawley rats aged 2 months with a body weights of 200-250 g[1]
Doses: 0.3, 1, 3, 30 mg/kg Route of Administration: Subcutanous injections Experimental Results: Specific c-fos gene expression was detected at all concentrations (0.3 mg/kg, 1 mg/kg, 3 mg/kg, 30 mg/kg) tested in frontal, parietal, perirhinal, temppo (oral gavage) piriform, insular, limbic, cingulate and occipital cortex. In vivo antipsychotic efficacy studies are conducted in rodent models. Panamesine is administered orally or intraperitoneally (1-30 mg/kg) to rats. Models include amphetamine-induced hyperlocomotion, PCP-induced hyperactivity, and prepulse inhibition (PPI) deficit models. c-fos expression in brain regions (nucleus accumbens, prefrontal cortex, striatum) is measured by immunohistochemistry. The c-fos expression pattern of panamesine is similar to that of atypical antipsychotics. Striatal D2-like dopamine receptor occupancy is also assessed. For open clinical trial protocols, patients with acute schizophrenia received panamesine at escalating doses. |
| ADME/Pharmacokinetics |
No specific PK data are reported for panamesine in supplier literature. As an orally active small molecule, panamesine is expected to have moderate oral bioavailability and to cross the blood-brain barrier to engage sigma receptors in the CNS. The compound has a molecular weight of approximately 350-450 g/mol (typical for sigma ligands). PK parameters (t1/2, Cmax, AUC) have not been published in available literature.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for panamesine in supplier literature. Preclinical animal studies demonstrated that panamesine is free of extrapyramidal side effects (catalepsy, EPS), a common toxicity associated with typical antipsychotics. In open clinical trials, panamesine was reported to be well-tolerated, but development was discontinued. No FDA approval has been granted. The compound is no longer in clinical development.
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| References | |
| Additional Infomation |
Panamesine is a small molecule drug. The INN stem "-mesine" in its name indicates that panamesine is a σ receptor ligand. The monoisotope molecular weight of panamesine is 426.18 Da.
Other information: Panamesine (EMD 57445) is a sigma receptor ligand that reached Phase 2 clinical trials for schizophrenia before development was discontinued. It is an atypical antipsychotic candidate with functional antidopaminergic activity but without extrapyramidal side effects. The compound is now available only as a research chemical for pharmacological studies. CAS number: 139225-22-2. It is not FDA-approved. Synonyms: EMD 57445. The compound is for research use only and not for human consumption. |
| Molecular Formula |
C23H26N2O6
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|---|---|
| Molecular Weight |
426.46
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| Exact Mass |
426.179
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| CAS # |
139225-22-2
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| PubChem CID |
3047810
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.343g/cm3
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| Boiling Point |
614.1ºC at 760 mmHg
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| Flash Point |
325.2ºC
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| Vapour Pressure |
6.17E-16mmHg at 25°C
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| Index of Refraction |
1.621
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| LogP |
2.735
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
632
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| Defined Atom Stereocenter Count |
1
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| SMILES |
COC1=CC=C(C=C1)N2C[C@@H](OC2=O)CN3CCC(CC3)(C4=CC5=C(C=C4)OCO5)O
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| InChi Key |
NINYZUDVKTUKIA-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C23H26N2O6/c1-28-18-5-3-17(4-6-18)25-14-19(31-22(25)26)13-24-10-8-23(27,9-11-24)16-2-7-20-21(12-16)30-15-29-20/h2-7,12,19,27H,8-11,13-15H2,1H3/t19-/m0/s1
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| Chemical Name |
(5S)-5-[[4-(1,3-benzodioxol-5-yl)-4-hydroxypiperidin-1-yl]methyl]-3-(4-methoxyphenyl)-1,3-oxazolidin-2-one
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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 |
| 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) |
DMSO: 125 mg/mL (293.11 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.79 mg/mL (8.89 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), suspension solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.9 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: ≥ 2.08 mg/mL (4.88 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3449 mL | 11.7244 mL | 23.4489 mL | |
| 5 mM | 0.4690 mL | 2.3449 mL | 4.6898 mL | |
| 10 mM | 0.2345 mL | 1.1724 mL | 2.3449 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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