| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
human GAT-1 (IC50 = 14 μM); rat GAT-1 (IC50 = 39 μM); rat GAT-2 (IC50 = 58 μM); human GAT-3 (IC50 = 119 μM); rat GAT-3 (IC50 = 378 μM)
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| ln Vitro |
Guvacine HCl has IC50s of 14 μM (human GAT-1), 39 μM (rat GAT-1), and 58 μM (rat GAT-2); 119 μM (human GAT-3); 378 μM (rat GAT-3) and 1870 μM (human BGT-3). It is a strong inhibitor of GABA transporters with moderate selectivity for cloned GABA transporters. Guvacine's affinity (IC50 > 1 mM) for hBGT-1 is low [1]. Guvacine hydrochloride is a strong inhibitor of GABA uptake, although it has little or no effect as a GABA receptor agonist and does not prevent sodium-dependent GABA binding [2]. Guvacine inhibits the absorption of GABA and β-alanine, with IC50s in the cat spinal cord of 23 ± 2 μM and 66 ± 11 μM, respectively, and in the rat cerebral cortex of 8 ± 1 μM and 123 ± 28 μM [3].
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| ln Vivo |
Arecaidine and Guvacine, constituents of the nut of Areca catechu, inhibited the uptake of GABA and beta-alanine, but not that of glycine, by slices of cat spinal cord. In cats anesthetised with pentobarbitone, electrophoretic arecaidine enhanced the inhibitory actions of GABA and beta-alanine, but not those of glycine or taurine, on the firing of spinal neurones. Similarly, electrophoretic guvacine enhanced the inhibition of spinal neurones by GABA but not that by glycine. The uptake of GABA by slices of cat cerebellum was inhibited by arecaidine, and the effect of electrophoretic GABA on the firing of cerebellar Purkinje cells was enhanced by electrophoretic arecaidine. When administered intravenously arecaidine failed to affect synaptic inhibitions considered to be mediated by GABA. Intravenous arecaidine had no effect on either spinal prolonged (presynaptic) inhibition (20mg/kg), dorsal root potentials (20mg/kg) or basket cell inhibition of Purkinje cells (250 mg/kg), although topical arecaidine (6.6-10 x 10(-3) M) blocked this latter inhibition. Large doses of arecaidine (1 g/kg subcutaneous) marginally reduced the lethal effects of bicuculline in mice but appeared to have little or no anticonvulsant activity [3].
Gamma-aminobutyric acid A receptor (GABA(A)R)-mediated postsynaptic currents (IPSCs) were recorded from dopaminergic neurons of the ventral tegmental area of young rats in acute brain slices and from mechanically dissociated neurons. Low concentrations (0.1-0.3 microm) of muscimol, a selective GABA(A)R agonist, increased the amplitude, and reduced the paired pulse ratio of evoked IPSCs. Moreover, muscimol increased the frequency but not the amplitude of spontaneous IPSCs (sIPSCs). These data point to a presynaptic locus of muscimol action. It is interesting that 1 microm muscimol caused an inhibition of sIPSCs, which was reversed to potentiation by the GABA(B) receptor antagonist CGP52432. Isoguvacine, a selective GABA(A)R agonist that belongs to a different class, mimicked the effects of muscimol on sIPSCs: it increased them at low ( |
| Animal Protocol |
Most of the chemicals including d(–)-2-amino-5-phospho-pentanoate (AP5), 6,7-dinitroquinoxaline-2,3-dione (DNQX), bicuculline (BIC), cadmium chloride, isoguvacine, furosemide, 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol (gaboxadol, or THIP), Guvacine hydrochloride, Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol enkephalin (DAMGO) and tetrodotoxin (TTX), Muscimol and CGP52432 were obtained commercially. The solutions, prepared before the experiment, were applied to a dissociated neuron with a Y-tube. This exchanged the external solution surrounding the neurons within 40 ms (Zhou et al. 2006). In experiments on brain slices, chemicals were added in known concentrations to the superfusate. The fact that 10 μm bicuculline blocked most IPSCs (in slices) within 90 s is an indication of the effective bath exchange time. [4]
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| References |
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| Additional Infomation |
The application of the GABA transporter blocker Guvacine (20 μm) significantly and reversibly increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in brain slices (Figs. 7A and 7C) without inducing significant postsynaptic currents (5 ± 1 pA). Guvacine (20 μm) significantly shifted the cumulative probability plot of consecutive sIPSC event intervals to the left (KS test, P < 0.001; Fig. 7B, top) and increased the sIPSC frequency by 72 ± 14% (n = 7, P = 0.001, Fig. 7B, top inset), but did not change the amplitude of sIPSCs (KS test, P > 0.5, Fig. 7B, bottom; 0 ± 3%, n = 7, P = 0.46, Fig. 7B, bottom inset). These results indicate that increased environmental GABA levels enhance GABAergic sIPSCs through presynaptic mechanisms in the developing brain. [4]
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| Molecular Formula |
C6H10BRNO2
|
|---|---|
| Molecular Weight |
208.05300
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| Exact Mass |
206.989
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| CAS # |
6027-92-5
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| Related CAS # |
Guvacine hydrochloride;6027-91-4;Guvacine;498-96-4
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| PubChem CID |
15560295
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| Appearance |
White to off-white solid
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| LogP |
1.277
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
10
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| Complexity |
151
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC(C1CNCCC=1)=O.Br
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| InChi Key |
CAQYXXITPFGYGT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H9NO2.BrH/c8-6(9)5-2-1-3-7-4-5;/h2,7H,1,3-4H2,(H,8,9);1H
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| Chemical Name |
1,2,3,6-tetrahydropyridine-5-carboxylic acid;hydrobromide
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| Synonyms |
guvacine hydrobromide; Guvacine (hydrobromide); 6027-92-5; SCHEMBL9569008; 1,2,3,6-tetrahydropyridine-5-carboxylic acid;hydrobromide
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (~240.3 mM; with ultrasonication)
H2O: ~25 mg/mL (~120.2 mM; with ultrasonication) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (12.02 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (12.02 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.8065 mL | 24.0327 mL | 48.0654 mL | |
| 5 mM | 0.9613 mL | 4.8065 mL | 9.6131 mL | |
| 10 mM | 0.4807 mL | 2.4033 mL | 4.8065 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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