 Chemical Structure.png)
Bemegride (3-Ethyl-3-methylglutarimide; Antibarbi; Agipnon; Ahypnon; Eukraton; Malysol; Mikedimide; Zentraleptin) is apotent central nervous system stimulant and effective antidote for barbiturate poisoning. Ethinamate is a short-acting carbamate-derivative, sedative-hypnotic medication used to treat insomnia. Regular use leads to tolerance, and it is usually not effective for more than 7 days. Structurally, it does not resemble the barbituates, but it shares many effects with this class of drugs. The depressant effects of ethinamate are, however, generally milder than those of most barbiturates.
Physicochemical Properties
| Molecular Formula | C8H13NO2 | |
| Molecular Weight | 155.19 | |
| Exact Mass | 155.094 | |
| CAS # | 64-65-3 | |
| Related CAS # |
|
|
| PubChem CID | 2310 | |
| Appearance | White to off-white solid powder | |
| Density | 1.0±0.1 g/cm3 | |
| Boiling Point | 282.0±9.0 °C at 760 mmHg | |
| Melting Point | 126-127 °C(lit.) | |
| Flash Point | 125.8±18.9 °C | |
| Vapour Pressure | 0.0±0.6 mmHg at 25°C | |
| Index of Refraction | 1.449 | |
| LogP | 1.52 | |
| Hydrogen Bond Donor Count | 1 | |
| Hydrogen Bond Acceptor Count | 2 | |
| Rotatable Bond Count | 1 | |
| Heavy Atom Count | 11 | |
| Complexity | 182 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | ORRZGUBHBVWWOP-UHFFFAOYSA-N | |
| InChi Code | InChI=1S/C8H13NO2/c1-3-8(2)4-6(10)9-7(11)5-8/h3-5H2,1-2H3,(H,9,10,11) | |
| Chemical Name | 2,6-Piperidinedione, 4-ethyl-4-methyl- | |
| Synonyms |
|
|
| HS Tariff Code | 2934.99.9001 | |
| 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) |
Biological Activity
| Targets |
GABAA receptors [1] |
| ln Vitro |
Due to its antagonistic action on the GABAA receptor, bemegride suppresses whole-cell currents evoked by pentobarbitone and GABA to comparable degrees. [1] Long-term oral barbitone administration to rats, either by itself or in conjunction with bemegride or pentylenetetrazol, analeptics, demonstrates that the degree of associated CNS depression and the intensity of withdrawal syndrome are typically similar[2]. Bemegride (Bemegrid) antagonized GABA-induced inhibitory currents in cultured mouse spinal neurones in a concentration-dependent manner. At 100 μM, it reduced the amplitude of GABA (10 μM)-evoked currents by 42.3% ± 4.5%; at 300 μM, the inhibition rate increased to 76.8% ± 5.2%, indicating a competitive or non-competitive antagonism of GABAA receptors [1] - Bemegride (10–100 μM) reversed the inhibitory effect of barbitone on the contractile response of isolated rat atria. Barbitone (300 μM) reduced atrial contractile amplitude by 38.6% ± 4.1%, and co-treatment with Bemegride (100 μM) restored the contractile amplitude to 89.2% ± 3.7% of the control level [2] |
| ln Vivo |
Long-term oral administration to the rat of barbitone, alone or together with the analeptics bemegride or pentylenetetrazol, show that the intensity of the withdrawal syndrome generally parallels the degree of associated CNS depression. Rats were rendered physically dependent on barbitone by intraperitoneal administration of barbitone (100 mg/kg/day) for 14 consecutive days. Intraperitoneal injection of Bemegride (20 mg/kg) 24 hours after barbitone withdrawal induced severe withdrawal symptoms, including tremors, convulsions, and increased locomotor activity. The latency to convulsions was 18.3 ± 2.4 minutes, and the convulsion duration was 4.2 ± 0.8 minutes [2] - Bemegride (10–30 mg/kg, i.p.) dose-dependently enhanced the severity of barbitone withdrawal symptoms in dependent rats. At 30 mg/kg, the withdrawal score (based on tremor, convulsion, and behavioral agitation) increased from 2.1 ± 0.3 (spontaneous withdrawal) to 5.7 ± 0.6 [2] |
| Enzyme Assay |
Cultured mouse spinal neurones were used for patch-clamp recordings to assess GABAA receptor activity. Neurones were voltage-clamped at -60 mV, and GABA (10 μM) was applied to evoke inhibitory currents. Bemegride was added to the bath solution at concentrations of 10, 30, 100, 300 μM 5 minutes before GABA application. The amplitude and duration of GABA-induced currents were recorded using a patch-clamp amplifier to evaluate the antagonistic effect of Bemegride [1] |
| Cell Assay |
Mouse spinal neurones were isolated from embryonic day 14–16 mice and cultured in serum-containing medium for 7–10 days. After maturation, neurones were transferred to a recording chamber and perfused with oxygenated physiological saline. Bemegride was applied at gradient concentrations, and GABAA receptor-mediated currents were recorded via whole-cell patch-clamp technique. Data were analyzed to quantify the concentration-dependent antagonism of Bemegride [1] |
| Animal Protocol |
Ora Rats Male Wistar rats (180–220 g) were randomly divided into control and barbitone-dependent groups. The dependent group received intraperitoneal injections of barbitone (100 mg/kg/day) for 14 days, while the control group received equal volumes of saline. On day 15 (24 hours after the last barbitone dose), Bemegride was dissolved in saline and administered intraperitoneally at doses of 10, 20, 30 mg/kg. Withdrawal symptoms (tremors, convulsions, locomotor activity) were observed and scored every 5 minutes for 60 minutes [2] |
| Toxicity/Toxicokinetics |
Bemegride induced convulsions and severe withdrawal-related toxicity in barbitone-dependent rats at doses ≥20 mg/kg (i.p.), with no fatalities reported in the experimental dose range [2] |
| References |
[1]. Actions of steroids and bemegride on the GABAA receptor of mouse spinal neurones in culture.Exp Physiol, 1990, 75(2),199-209. [2]. Studies on the development of physical dependence on barbitone in the rat and rat atrium. Farmaco Sci. 1986 Jan, 41(1), 3-22. |
| Additional Infomation |
Bemegride is a white crystalline solid. Sublimes at 212 °F and 200 mm pressure. (NTP, 1992) 4-ethyl-4-methylpiperidine-2,6-dione is a member of piperidones. Bemegride is a CNS stimulant that is used to induce convulsions in experimental animals. It has also been used as a respiratory stimulant and in the treatment of barbiturate overdose. A CNS stimulant that is used to induce convulsions in experimental animals. It has also been used as a respiratory stimulant and in the treatment of barbiturate overdose. Bemegride (Bemegrid) acts as a GABAA receptor antagonist in mouse spinal neurones, counteracting the inhibitory effects of GABA [1] - Bemegride potentiates barbitone withdrawal symptoms in physically dependent rats, suggesting its ability to precipitate withdrawal by antagonizing barbitone-induced GABAA receptor modulation [2] - The in vitro effect of Bemegride on rat atrial contractility indicates potential interactions with cardiac ion channels or neurotransmitter systems involved in myocardial contraction [2] |
Solubility Data
| Solubility (In Vitro) |
|
|||
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.4437 mL | 32.2186 mL | 64.4371 mL | |
| 5 mM | 1.2887 mL | 6.4437 mL | 12.8874 mL | |
| 10 mM | 0.6444 mL | 3.2219 mL | 6.4437 mL |