Guvacine hydrochloride

Names

[ Name ]:
Guvacine hydrochloride

[Synonym ]:
GUVACINE HYDROCHLORIDE &3-Pyridinecarboxylic acid,1,2,5,6-tetrahydro-,hydrochloride
1,2,5,6-Tetrahydro-pyridin-3-carbonsaeure,Hydrochlorid
1,2,5,6-Tetrahydro-3-pyridinecarboxylic Acid Hydrochloride
Dilazep dihydrochloride
Guvacine hydrochloride
1,2,5,6-Tetrahydro
GABA UPTAK
1,2,5,6-Tetrahydropyridine-3-carboxylic acid hydrochloride
1,2,5,6-tetrahydro-3-pyridinecarboxylic acid,hydrochloride salt

Biological Activity

[Description]:

Guvacine hydrochloride is an alkaloid from the nut of Areca catechu, 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).

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> GABA Receptor

Signaling Pathways >> Neuronal Signaling >> GABA Receptor

Natural Products >> Alkaloid

Research Areas >> Neurological Disease

[Target]

IC50: 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), 1870 μM (human BGT-3)[1]

[In Vitro]

Guvacine hydrochloride is a potent inhibitor of GABA transporter, dispalys modest selectivity forcloned 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). Guvacine has low affinity at hBGT-1 (IC50 >1 mM)[1]. Guvacine hydrochloride is a potent inhibitor of GABA uptake, but does not inhibit sodium-independent GABA binding, and is weak or inactive as a GABA receptor agonist[2]. Guvacine inhibits the uptake GABA and β-alanine with IC50s of 23 ± 2 μM, 66 ± 11 μM in the Cat spinal cord, and 8 ± 1 μM, 123 ± 28 μM in the rat cerebral cortex, respectively[3].

[Cell Assay]

Cells grown in 24-well plates are washed 3 × with Hepes-buffered saline (HBS, in mM: NaC1, 150; Hepes, 20; CaCl2, 1; glucose, 10; KC1, 5; MgCl2, 1; pH 7.4) and allowed to equilibrate on a 37°C slide warmer. After 10 min the medium is removed and unlabeled drugs (Guvacine , etc.) in HBS are added (450 μL/well). Transport is initiated by adding 50 μL per well of a concentrated solution of [3H]GABA in HBS (final concentration = 50 nM). Non-specific uptake is defined in parallel wells with 1 mM unlabeled GABA, and is subtracted from total uptake to yield specific uptake; all data represent specific uptake. Plates are incubated at 37°C for 10 min, then washed rapidly 3 × with ice-cold HBS, using a 24-position plate washer. Cells are solubilized with 0.05% sodium deoxycholate/0.1 N NaOH (0.25 mL/well), an aliquot neutralized with 1 N HC1, and radioactivity is determined by scintillation counting. Protein is quantified in an aliquot of the solubilized cells using a BIO-RAD protein assay kit[1].

[References]

[1]. Borden LA, et al. Tiagabine, SK&F 89976-A, CI-966, and NNC-711 are selective for the cloned GABA transporter GAT-1. Eur J Pharmacol. 1994 Oct 14;269(2):219-24.

[2]. Krogsgaard-Larsen P, et al. Structure-activity studies on the inhibition of GABA binding to rat brain membranes by muscimol and related compounds. J Neurochem. 1978 Jun;30(6):1377-82.

[3]. Lodge D, et al. Effects of the Areca nut constituents arecaidine and guvacine on the action of GABA in the cat central nervous system. Brain Res. 1977 Nov 18;136(3):513-22.

[Related Small Molecules]

Chemical & Physical Properties

[ Molecular Formula ]:
C₆H₁₀ClNO₂

[ Molecular Weight ]:
163.60200

[ Exact Mass ]:
163.04000

[ PSA ]:
49.33000

[ LogP ]:
1.12150

[ Storage condition ]:
2-8℃

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi

[ Risk Phrases ]:
36/37/38

[ Safety Phrases ]:
26-36

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2933399090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933399090

[ Summary ]:
2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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