| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Guvacine HCl, the hydrochloride salt of Guvacine, is an alkaloid isolated from the nut of Areca catechu which acts as an inhibitor of GABA transporter, and dispalys modest selectivity for cloned GABA transporters with IC50s of 14 μM (human GAT-1), 39 μM (rat GAT-1), 58 μM (rat GAT-2), 119 μM (human GAT-3), 378 μM (rat GAT-3), and 1870 μM (human BGT-3).
| 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 Guvacine (20 μm), a GABA transporter blocker, induced a robust and reversible increase in the frequency of sIPSCs recorded in slices (Fig. 7A and C) without inducing a significant postsynaptic current (5 ± 1 pA). Guvacine (20 μm) induced a large leftward shift in the cumulative probability plot of inter-event intervals between successive sIPSCs (K-S test, P < 0.001; upper panel in Fig. 7B) and an increase of 72 ± 14% (n = 7, P = 0.001, upper panel inset in Fig. 7B) in sIPSC frequency, while it did not alter sIPSC amplitude (K-S test, P > 0.5, lower panel in Fig. 7B; 0 ± 3%, n = 7, P = 0.46, lower panel inset in Fig. 7B). These results suggest that an increase in ambient GABA level enhances GABAergic sIPSCs via a presynaptic mechanism in the developing brain.[4]
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| Molecular Formula |
C6H10CLNO2
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|---|---|
| Molecular Weight |
163.6021
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| Exact Mass |
163.04
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| Elemental Analysis |
C, 44.05; H, 6.16; Cl, 21.67; N, 8.56; O, 19.56
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| CAS # |
6027-91-4
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| Related CAS # |
Guvacine;498-96-4;Guvacine hydrobromide;6027-92-5; 6197-39-3 (Norarecoline HCl); 6027-91-4 (HCl)
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| PubChem CID |
11957555
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| Appearance |
White to off-white solid powder
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| LogP |
1.121
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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 |
C1CNCC(=C1)C(=O)O.Cl
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| InChi Key |
FGNUNVVTHHKDAM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H9NO2.ClH/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;hydrochloride
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| Synonyms |
1,2,5,6-tetrahydropyridine-3-carboxylic acid hydrochloride; 637-422-5; Guvacine hydrochloride; 6027-91-4; 1,2,5,6-Tetrahydro-pyridine-3-carboxylic acid hydrochloride; Guvacine HCl; 1,2,5,6-Tetrahydro-3-pyridinecarboxylic Acid Hydrochloride; 1,2,3,6-Tetrahydropyridine-5-carboxylic acid 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 : ~41.67 mg/mL (~254.71 mM)
DMSO : ~1 mg/mL (~6.11 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 25 mg/mL (152.81 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.1125 mL | 30.5623 mL | 61.1247 mL | |
| 5 mM | 1.2225 mL | 6.1125 mL | 12.2249 mL | |
| 10 mM | 0.6112 mL | 3.0562 mL | 6.1125 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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