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| Other Sizes |
| Targets |
Tetramisole is a well-documented inhibitor of tissue non-specific alkaline phosphatase (TNAP). It is the racemic mixture of levamisole (levorotatory) and dexamisole (dextrorotary). Levamisole is the active TNAP inhibitor, while dexamisole has no significant effect on this enzyme. [1]
- Tetramisole and levamisole may also block voltage-dependent sodium channels, as suggested by decreased axonal conduction velocity and reduced action potential rate of rise. [1] - Tetramisole and levamisole may modulate ganglionic acetylcholine receptors (α3β2 and α3β4) and inhibit noradrenaline reuptake in the peripheral nervous system. [1] |
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| ln Vitro |
In mouse somatosensory cortex slices, tetramisole (0.1–5 mM) reduced the amplitude of antidromic population spikes in a dose-dependent manner (IC₅₀ = 0.73 ± 0.08 mM, Hill coefficient 3.04). [1]
- Orthodromic responses were more sensitive, with an IC₅₀ of 0.41 ± 0.15 mM (Hill coefficient 2.97). [1] - Tetramisole (0.5–2 mM) increased the latency of antidromic population spikes (up to +110% at 2 mM), indicating slowed axonal conduction velocity. [1] - In corpus callosum recordings, tetramisole (1 mM) reduced axonal population spike amplitude to 56 ± 7% of control and increased latency by 43 ± 10%. [1] - Tetramisole (1 mM) prolonged action potential duration and reduced the maximum rate of rise (dV/dtmax) to 48% of control in intracellular recordings, suggesting sodium channel blockade. [1] - The effects of tetramisole were not stereo-specific: levamisole (0.5 and 1 mM) produced similar reductions in antidromic response amplitude as tetramisole at the same concentrations. [1] - Exogenous pyridoxal (10 μM) or adenosine (100 μM) did not reverse the effects of tetramisole (1 mM). [1] - MLS-0038949 (10 μM), another TNAP inhibitor, had no effect on antidromic responses, confirming that tetramisole’s effects are not mediated by TNAP inhibition. [1] |
| Enzyme Assay |
The study references prior biochemical studies reporting IC₅₀ values for TNAP inhibition by levamisole in the range of 10–70 μM, with a Hill coefficient close to 1. [1]
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| Cell Assay |
Brain slice preparation: Adult mouse somatosensory cortex slices (400 μm thick) were cut in cold modified ACSF (Ca²⁺-free, 10 mM Mg²⁺). Slices were stored in oxygenated ACSF (Ca²⁺ 1.2 mM) and recorded at 33–34°C. [1]
- Extracellular recordings: Local field potentials (LFPs) were recorded in layer 4 and supragranular layers using glass micropipettes (2–7 MΩ) or tungsten microelectrodes. Electrical stimulation (0.2–0.3 ms pulses, 50–180 μA) was applied in white matter or corpus callosum. Responses were averaged over 1 min (6–30 sweeps). [1] - Intracellular recordings: Sharp electrodes (60–100 MΩ) filled with 3 M K-acetate were used. Action potentials were evoked by current injection. [1] - Chemicals were dissolved in ACSF and perfused at 2.5–3.75 mL/min. Drug effects were monitored for 20–30 min. [1] |
| Animal Protocol |
Adult female wild-type mice (>2 months old) were anesthetized with isoflurane and killed by decapitation. Brains were rapidly removed in cold modified ACSF. [1]
- No in vivo drug administration experiments were conducted. All experiments were performed on ex vivo brain slices. [1] Adult female wild-type mice (>2 months old) were anesthetized with isoflurane and killed by decapitation. Brains were rapidly removed in cold modified ACSF. [1] - No in vivo drug administration experiments were conducted. All experiments were performed on ex vivo brain slices. [1] |
| ADME/Pharmacokinetics |
The study references prior literature indicating that plasma levamisole concentrations in humans receiving therapeutic doses are typically <5 μM, though accumulation with repeated dosing may occur. [1]
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| Toxicity/Toxicokinetics |
At concentrations ≥ 0.5–1 mM, tetramisole and levamisole significantly suppressed neuronal activity. [1]
- Chronic levamisole use in humans has been associated with serious side effects including epileptic seizures, multifocal inflammatory leukoencephalopathy, agranulocytosis, and cutaneous vasculitis. [1] - In dogs, chronic levamisole intake resulted in mononuclear cell infiltration and demyelination in the brain. [1] - Tetramisole at 2 mM nearly completely suppressed antidromic responses (4.4% of control). [1] - The study notes that tetramisole and levamisole are currently used as adulterants in illicit cocaine, leading to resurgence of these toxic effects. [1] |
| References | |
| Additional Infomation |
Tetramisole hydrochloride is an organic molecular entity.
See also: Levoimidazole hydrochloride (note moved to). Tetramisole was originally isolated for its anthelmintic properties and is effective against intestinal and pulmonary nematodes. Levamisole is the active enantiomer for anthelmintic activity. [1] - Tetramisole and levamisole have been used as immunostimulants, though their efficacy is limited and they have been discontinued in most countries due to severe side effects. [1] - This study demonstrates for the first time that tetramisole and levamisole suppress neuronal activity independently of TNAP inhibition, likely through blockade of voltage-dependent sodium channels. [1] - The findings suggest that tetramisole and levamisole should not be used solely as TNAP inhibitors in living excitable cells, as they also block activity-dependent processes. [1] - Possible targets in the nervous system include TNAP, voltage-dependent sodium channels, ganglionic nicotinic acetylcholine receptors, and noradrenaline reuptake mechanisms. [1] - The neurological side effects of levamisole (epilepsy, leukoencephalopathy) may be related to TNAP inhibition and altered GABA/adenosine metabolism, as well as purinergic signaling dysregulation. [1] |
| Molecular Formula |
C11H12N2S.HCL
|
|---|---|
| Molecular Weight |
240.75232
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| Exact Mass |
240.048
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| CAS # |
5086-74-8
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| Related CAS # |
Levamisole;14769-73-4;Dexamisole;14769-74-5
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| PubChem CID |
68628
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| Appearance |
White to off-white solid powder
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| Boiling Point |
344.4ºC at 760 mmHg
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| Melting Point |
266-267ºC
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| Flash Point |
162.1ºC
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| LogP |
2.321
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
15
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| Complexity |
246
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LAZPBGZRMVRFKY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H12N2S.ClH/c1-2-4-9(5-3-1)10-8-13-6-7-14-11(13)12-10;/h1-5,10H,6-8H2;1H
|
| Chemical Name |
6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole;hydrochloride
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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. |
| 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) |
H2O : ~100 mg/mL (~415.37 mM)
DMSO : ~10 mg/mL (~41.54 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (4.15 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (4.15 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 10.0 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: ≥ 1 mg/mL (4.15 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 110 mg/mL (456.91 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1537 mL | 20.7684 mL | 41.5369 mL | |
| 5 mM | 0.8307 mL | 4.1537 mL | 8.3074 mL | |
| 10 mM | 0.4154 mL | 2.0768 mL | 4.1537 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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