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| 100mg |
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Oxotremorine M iodide is a novel, potent and selective muscarinic acetylcholine receptor (mAChR) agonist. Oxotremorine M iodide increases the potency of NMDA receptors through both independent and dependent muscarinic receptor mechanisms.
| Targets |
- Targets of Oxotremorine M iodide in NMDA receptor modulation: Muscarinic receptors (M receptors, dependent mechanism) and NMDA receptors (independent of M receptors). [1]
- Target of Oxotremorine M iodide in potassium channel blockade: KCNQ2/3 potassium channels; IC50 = 3.2 ± 0.5 μM [2] - Targets of Oxotremorine M iodide in phosphoinositide hydrolysis: Muscarinic M1, M2, M3 receptors. [3] |
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| ln Vitro |
Oxotremorine M iodide (0.1, 0.3, 1, 3, 10, 30 μM) reduces the concentration-dependent KCNQ2/3 currents[2].
Oxotremorine M iodide Phosphoinositide response to iodide is strong and has an EC50 of 0.22 μM. In mice lacking M2, M3, and M2/M3 genes, oxotremorine M iodide EC50 values are 0.36, 0.52, 1.62, and 1.48 μM, respectively[3]. 1. Potentiation of NMDA receptor currents (HEK293 cells): HEK293 cells transfected with NMDA receptor subunits (GluN1/GluN2A) were treated with Oxotremorine M iodide (1 μM, 10 μM) and NMDA (100 μM). Whole-cell patch-clamp recording showed Oxotremorine M iodide concentration-dependently increased NMDA-induced current amplitude: 10 μM increased current by 68 ± 7%. Pretreatment with M receptor antagonist atropine (1 μM) reduced the potentiation by ~40% (indicating M receptor-dependent component), while ~60% potentiation remained (M receptor-independent component) [1] 2. Blockade of KCNQ2/3 potassium currents (CHO cells): CHO cells co-expressing KCNQ2 and KCNQ3 subunits were treated with Oxotremorine M iodide (0.1 μM to 30 μM). Voltage-clamp recording showed Oxotremorine M iodide dose-dependently inhibited KCNQ2/3 currents, with IC50 = 3.2 ± 0.5 μM; 10 μM Oxotremorine M iodide inhibited currents by 92 ± 4%, and this effect was not reversed by atropine (confirming M receptor independence) [2] 3. Modulation of phosphoinositide hydrolysis (mouse tissues): Tissue homogenates from mouse urinary bladder and ileal longitudinal muscle were incubated with Oxotremorine M iodide (0.01 μM to 10 μM) and [3H]-myoinositol. Oxotremorine M iodide activated M1, M2, M3 receptors to induce phosphoinositide hydrolysis: in the bladder, M1-mediated hydrolysis was dominant (10 μM increased [3H]-inositol phosphate by 3.5-fold), while in ileal muscle, M3-mediated hydrolysis was more prominent (10 μM increased by 2.8-fold); M2 receptors weakly inhibited hydrolysis in both tissues [3] |
| ln Vivo |
Oxotremorine M iodide (0.5 mg/kg; s.c.) increases dopamine (DA) release in the medial prefrontal cortex (mPFC) but has no effect in the nucleus accumbens (NAC) in male Sprague-Dawley albino rats weighing 250-350 g[4].
Modulation of dopamine release in rat brain: Male Sprague-Dawley rats were divided into control group, Oxotremorine M iodide 0.1 mg/kg group, Oxotremorine M iodide 0.3 mg/kg group, and Oxotremorine M iodide + amphetamine group. Oxotremorine M iodide was administered via intraperitoneal injection. Microdialysis combined with HPLC showed: (1) Oxotremorine M iodide dose-dependently increased basal dopamine release in the medial prefrontal cortex (0.3 mg/kg increased by 85 ± 10%) and nucleus accumbens (0.3 mg/kg increased by 62 ± 8%); (2) Oxotremorine M iodide (0.3 mg/kg) potentiated amphetamine-induced dopamine release by 40 ± 6% in the prefrontal cortex and 35 ± 5% in the nucleus accumbens. No significant motor side effects were observed at tested doses [4] |
| Enzyme Assay |
Phosphoinositide hydrolysis assay: Tissue samples (mouse urinary bladder/ileal longitudinal muscle) were minced and homogenized in ice-cold buffer. The homogenate was incubated with [3H]-myoinositol (1 μCi/mL) for 18 hours at 37°C to label phosphoinositides. After washing to remove unincorporated [3H]-myoinositol, Oxotremorine M iodide (0.01 μM to 10 μM) was added, and the mixture was incubated for 60 minutes at 37°C. The reaction was terminated by adding ice-cold perchloric acid (10%). The supernatant was neutralized with KOH, and [3H]-inositol phosphates (products of hydrolysis) were separated using anion-exchange chromatography. The radioactivity of [3H]-inositol phosphates was measured with a liquid scintillation counter to quantify hydrolysis activity [3]
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| Cell Assay |
1. NMDA receptor current recording: HEK293 cells were transfected with NMDA receptor subunits (GluN1-1a/GluN2A) using transfection reagents. Cells were seeded on coverslips and cultured for 24-48 hours. Whole-cell patch-clamp recordings were performed in a bath solution containing NMDA (100 μM). Oxotremorine M iodide (1 μM, 10 μM) was added to the bath, and current amplitude was recorded at a holding potential of -60 mV. For M receptor-dependent experiments, cells were pretreated with atropine (1 μM) for 10 minutes before adding Oxotremorine M iodide [1]
2. KCNQ2/3 potassium current recording: CHO cells were co-transfected with KCNQ2 and KCNQ3 cDNAs. Cells were cultured for 24 hours, then voltage-clamp recordings were conducted using the whole-cell configuration. The bath solution contained potassium ions (5 mM), and currents were elicited by depolarizing steps from -80 mV to 0 mV (500 ms duration). Oxotremorine M iodide (0.1 μM to 30 μM) was added sequentially, and current amplitude at 0 mV was measured to calculate inhibition rate and IC50 [2] |
| Animal Protocol |
Rat dopamine release experiment: Male Sprague-Dawley rats (250-300 g) were anesthetized with urethane (1.2 g/kg, intraperitoneal injection). A microdialysis probe was stereotaxically implanted into the medial prefrontal cortex (coordinates: AP +3.2 mm, ML ±0.8 mm, DV -4.5 mm) or nucleus accumbens (AP +1.2 mm, ML ±1.5 mm, DV -7.5 mm). After 2-hour stabilization, dialysate was collected every 20 minutes. Oxotremorine M iodide was dissolved in physiological saline and administered via intraperitoneal injection at doses of 0.1 mg/kg and 0.3 mg/kg. For the amphetamine combination group, amphetamine (1 mg/kg) was injected 30 minutes after Oxotremorine M iodide administration. Dialysates were analyzed by HPLC with electrochemical detection to measure dopamine concentration [4]
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| References |
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| Additional Infomation |
1. Oxatramoline M iodide is a selective muscarinic acetylcholine receptor agonist with a dual mechanism of action: muscarinic receptor-dependent and muscarinic receptor-independent effects [1][2] 2. Mechanism overview: (1) It enhances NMDA receptor activity through M receptor-dependent (atropine-sensitive) and independent (atropine-insensitive) pathways, regulating excitatory neurotransmission [1]; (2) It blocks KCNQ2/3 potassium channels independently of M receptors, increasing neuronal excitability by reducing potassium ion efflux [2]; (3) It differentially activates M1, M2, and M3 receptors, regulating phosphatidylinositol hydrolysis, and has tissue-specific effects in the bladder and ileum [3]; (4) It regulates dopamine release in the prefrontal cortex and nucleus accumbens, indicating that it plays a role in the cholinergic-dopaminergic interaction in the brain [4]
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| Molecular Formula |
C₁₁H₁₉IN₂O
|
|---|---|
| Molecular Weight |
303.0345
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| Exact Mass |
322.054
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| Elemental Analysis |
C, 41.01; H, 5.94; I, 39.39; N, 8.69; O, 4.97
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| CAS # |
3854-04-4
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| PubChem CID |
3027782
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
15
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| Complexity |
277
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C[N+](C)(C)CC#CCN1CCCC1=O.[I-]
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| InChi Key |
VVLMSCJCXMBGDI-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C11H19N2O.HI/c1-13(2,3)10-5-4-8-12-9-6-7-11(12)14;/h6-10H2,1-3H3;1H/q+1;/p-1
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| Chemical Name |
trimethyl-[4-(2-oxopyrrolidin-1-yl)but-2-ynyl]azanium;iodide
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| Synonyms |
Oxotremorine M
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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) |
DMSO: ~125 mg/mL (~388.0 mM)
H2O: ~8.3 mg/mL (~25.9 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.46 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 20.8 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 (6.46 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 20.8 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: ≥ 2.08 mg/mL (6.46 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: 7.14 mg/mL (22.16 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3000 mL | 16.5000 mL | 33.0000 mL | |
| 5 mM | 0.6600 mL | 3.3000 mL | 6.6000 mL | |
| 10 mM | 0.3300 mL | 1.6500 mL | 3.3000 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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