| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
GABA receptor
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|---|---|
| ln Vitro |
Bicuculline itself is difficult to use because it is unstable at physiological pH (Ref. 8) and not very soluble in aqueous solutions. This can be a problem, particularly for iontophoresis and superfusion of in vitro preparations and so, in response to this, the quaternary N-methyl derivative was synthesized and various salts (bicuculline methiodide, methochloride and methobromide, which we will refer to as BIC salts) were made available. The base of bicuculline and BIC salts was used extensively as specific GABAA receptor antagonists. It should be noted that recent experiments using recombinant receptors have modified the classical view of the interaction of bicuculline and SR95531 with the GABAA receptor. Indeed, it has been suggested that both compounds might have a negative allosteric effect (i.e. be inverse agonists) rather than (or in addition to) being competitive antagonists.
Several reports have shown that bicuculline and BIC salts also affect other neurotransmitter systems (e.g. the cholinergic system) and possibly ion channels, but results from these studies, which are summarized in Table 1, have been overlooked by many investigators. There appear to be two main reasons for this. First, actions on the cholinergic system should be easily distinguished from the GABAergic effect (for example, block of nicotinic responses will have an inhibitory effect instead of the classical excitatory effect of bicuculline) and second, some of the drugs' effects (e.g. effects on spinal cord neurones) occurred at rather high concentrations [1]. |
| ln Vivo |
(-)-BicucuLlinemethobromide (0.6nmol/rat) takes off the anti-allodynia action of Neurotropin [2]. IV (50-100 NU/kg) doses of Neurotropin elicited an antiallodynic action in L5-SNL rats. Moreover, intracerebroventricular (400 mNU/rat), but not intrathecal, injection of Neurotropin inhibited allodynia. The antiallodynic action of Neurotropin (100 NU/kg, IV) was antagonized by intrathecal injections of yohimbine (10 nmol/rat), ketanserin (30 nmol/rat), MDL72,222(30 nmol/rat), bicuculline (0.6 nmol/rat) and CGP35348 (30 nmol/rat). On the other hand, the antiallodynic action of intrathecally injected m-CPBG (5-HT(3) receptor agonist) was reversed by intrathecal injection of bicuculline and CGP35348, suggesting interaction of 5-HT(3) receptors and spinal inhibitory (GABAergic) interneurons. Conclusions: These results suggest that the antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems, such as the noradrenergic and serotonergic systems, which project from supraspinal sites to the spinal dorsal horn. In addition, activation of inhibitory GABAergic interneurons via 5-HT(3) receptors by serotonin released in the spinal dorsal horn may also be involved in the antiallodynic action of Neurotropin [2].
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| Cell Assay |
Block of Ca2+-activated K+ currents by BIC salts (bicuculline methiodide, methochloride and methobromide) in mammalian neurones. These experiments were performed on brain slices using either intracellular recordings (a, b) or whole-cell patch-clamp recordings (c). a: Concentration-dependent blockade of the apamin-sensitive afterhyperpolarization (AHP) by a BIC salt in a mesencephalic dopaminergic neurone. Note that the maximal effect of bicuculline methochloride (BMC) is similar to the one of a maximally active concentration of apamin. b: Comparison of the potency of BMC as a GABAA receptor antagonist (circles) and as a blocker of the AHP (squares) in dopaminergic neurones. The antagonism at GABAA receptors was estimated by the ability of the BIC salts to antagonize the increase in conductance induced by muscimol (3 μm) (not shown). Note that the two curves partially overlap. c: Concentration-dependent enhancement by a BIC salt of the rebound low-threshold spike in a thalamic reticular nucleus neurone. This effect is due to a block of the apamin-sensitive current. Note that it occurs at concentrations similar to the ones that block this current in dopaminergic neurones [1].
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| Animal Protocol |
Animal/Disease Models: Rat L5-SNL model [2]
Doses: 0.6nmol/rat Route of Administration: Intrathecal injection, Neurotropin (100 NU/kg, intravenous (iv) (iv)injection) 5 minutes before administration Experimental Results:The anti-allodynia effect of Neurotropin is weakened effect. The left fifth lumbar nerve of rats was tightly ligated with silk sutures under pentobarbital anesthesia. Mechanical allodynia was confirmed by measuring the hindpaw withdrawal threshold in response to application of von Frey filaments. Behavioral tests were performed at 28 days after nerve ligation. Neurotropin was administered IV, intrathecally or intracerebroventricularly in L5 spinal nerve ligation (L5-SNL) rats. We examined the effects of noradrenergic, serotonergic and gamma-aminobutyric acid (GABA)ergic antagonists on the antiallodynic action of Neurotropin in L5-SNL rats. Yohimbine hydrochloride (yohimbine) was used as an alpha(2) adrenoceptor antagonist, ketanserin tartrate (ketanserin) as a 5-HT(2A) receptor antagonist, MDL72,222 as a 5-HT(3) receptor antagonist, (-)-bicuculline methobromide (bicuculline) as a GABA(A) receptor antagonist, and CGP35,348 as a GABA(B) receptor antagonist, and intrathecally injected. [2] |
| References |
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| Additional Infomation |
Neurotropin, a nonprotein extract isolated from inflamed skin of rabbits inoculated with vaccinia virus, is widely used in Japan to treat chronic pain such as neuropathic pain. Although some studies have been conducted on the mechanism of the antiallodynic action of Neurotropin, this mechanism has yet to be adequately clarified.[2]
|
| Molecular Formula |
C21H20NO6+.BR-
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|---|---|
| Molecular Weight |
462.2906
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| Exact Mass |
461.047
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| CAS # |
73604-30-5
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| Related CAS # |
Bicuculline methiodide;40709-69-1;Bicuculline;485-49-4;(-)-Bicuculline methochloride;53552-05-9;Bicuculline methobromide;66016-70-4
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| PubChem CID |
171729
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
29
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| Complexity |
655
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BWXCECYGGMGBHD-UHFFFAOYSA-M
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| InChi Code |
InChI=1S/C21H20NO6.BrH/c1-22(2)6-5-11-7-15-16(26-9-25-15)8-13(11)18(22)19-12-3-4-14-20(27-10-24-14)17(12)21(23)28-19;/h3-4,7-8,18-19H,5-6,9-10H2,1-2H3;1H/q+1;/p-1
|
| Chemical Name |
6-(6,6-dimethyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-6-ium-5-yl)-6H-furo[3,4-g][1,3]benzodioxol-8-one;bromide
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| Synonyms |
(-)-BICUCULLINE METHOBROMIDE; 73604-30-5; 6-(6,6-dimethyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-6-ium-5-yl)-6H-furo[3,4-g][1,3]benzodioxol-8-one;bromide; (-)-Bicuculline Methbromide; [R-(R*,S*)]-5-(6,8-Dihydro-8-oxofuro[3,4-e]-1,3-benzodioxol-6-yl)-5,6,7,8-tetrahydro-6,6-dimethyl-1,3-dioxolo[4,5-g]isoquinolinium bromide; d-Bicuculline (methobromide); (R-(R*,S*))-5-(6,8-Dihydro-8-oxofuro(3,4-e)-1,3-benzodioxol-6-yl)-5,6,7,8-tetrahydro-6,6-dimethyl-1,3-dioxolo(4,5-g)isoquinolinium bromide; C21H20BrNO6;
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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 : ~50 mg/mL (~108.16 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.41 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 25.0 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: ≥ 2.5 mg/mL (5.41 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 25.0 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: ≥ 2.5 mg/mL (5.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1631 mL | 10.8157 mL | 21.6314 mL | |
| 5 mM | 0.4326 mL | 2.1631 mL | 4.3263 mL | |
| 10 mM | 0.2163 mL | 1.0816 mL | 2.1631 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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