CGP52432 is a GABAB receptor antagonist, with an IC50 of 85 nM, 35- and 100-fold lower than at the receptors regulating somatostatin and glutamate overflow, respectively[1]. CGP52432 exhibited intrinsic activity only in the hippocampus; in spinal cord, it behaved exclusively as a silent orthosteric antagonist by blocking the release inhibition brought about by (-)-baclofen[2]. CGP52432 (10, 30 mg/kg) shows no effect on the total arm entries and total head dips of mice on the elevated-plus maze[3]. Treatment with the GABAB receptor antagonist CGP52432 (100 nmol/kg, i.v., or 1 nmol/kg, i.c.v.) abolished the suppressive effects of 50 μmol/kg, i.v., GABA on enhanced renal sympathetic nerve activity (RSNA) during ischaemia, leading to elimination of the renoprotective effects of GABA[4]. CGP52432 (a GABAB receptor antagonist) at intravenous dosages of 0.1-1 mg/kg completely removed the TNS (tibial nerve stimulation) inhibition in female cats but had no effect in male cats. CGP52432 administered intravenously also had no effect on control bladder capacity or the pudendal inhibition of bladder overactivity[5].
CGP52432 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Neural stem cells (NSCs)
1 μM
24 hours
CGP dose-dependently enhanced the cell viability of NSCs, and immunofluorescence staining showed that CGP promoted the proliferation of NSCs
Stem Cell Res Ther. 2021 Jan 7;12(1):22.
Rat spinal cord dorsal horn slices
1-30 μM
6 minutes
To investigate the effect of CGP52432 on GABA and glutamate release, results showed that CGP52432 significantly increased the release of GABA and glutamate and reversed the inhibitory effect of (-)-baclofen.
Br J Pharmacol. 1996 Jul;118(5):1153-60.
Dopaminergic neurons
1 μM
CGP52432 reversed the inhibition of sIPSCs by 1 μM muscimol and enhanced the increase in sIPSC frequency induced by 0.3 μM muscimol
J Physiol. 2007 May 1;580(Pt.3):731-43.
Rat hippocampal CA3 pyramidal cells
2 µM
Investigated the effect of GABAB receptor antagonist CGP52432 on unitary IPSPs, showing no significant effect on amplitude or paired-pulse depression
J Physiol. 2000 Oct 1;528 Pt 1(Pt 1):123-30.
PT neurons
2.5 µM
7 min
Blocking GABAB receptors to study the effect of ACh on excitatory synaptic transmission in PT neurons. Results showed that GABA receptor blockade did not affect the enhancement of excitatory synaptic transmission by ACh in PT neurons.
J Neurosci. 2024 Jan 17;44(3):e1388232023.
CGP52432 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
Bilateral common carotid artery occlusion (BCCAO)-induced cerebral ischemia model
Intraperitoneal injection
10 mg/kg
Once daily for 7 or 14 days
CGP significantly improved spatial learning and memory disorders caused by CI, and enhanced the proliferation of neural stem cells (NSCs), the number of immature neurons, and the differentiation from newborn cells to neurons
Stem Cell Res Ther. 2021 Jan 7;12(1):22.
Mice
Observational fear model
Bath perfusion in brain slices
10 μM
Single administration, lasting 10 minutes
To investigate the effect of CGP52432 on GABAB receptor-mediated inhibitory synaptic transmission after observational fear training. Results showed that CGP52432 abolished the opposing effects of observational fear training on IPSC dynamics in PV and SOM interneurons.
Neuropsychopharmacology. 2017 May;42(6):1272-1283
Rat
Dentate gyrus hilar mossy cells
Bath application
10 μM
To investigate the effect of CGP52432 on CCh-mediated inhibitory synaptic transmission, finding that CGP52432 reverses NO-711-mediated inhibition but is ineffective against high-concentration CCh-mediated inhibition.
J Physiol. 2010 Aug 1;588(Pt 15):2801-22
Rat
Awake freely moving rats
Intrathecal injection
100 nmol
Single injection
To investigate the inhibitory effect of CGP52432 on hypotension induced by Sar9 and baclofen. Results showed that CGP52432 significantly reduced the hypotension evoked by Sar9 and baclofen.
Br J Pharmacol. 2002 Aug;136(8):1169-77
Rats
Freely moving rats
Local infusion
50 µM
Continuous infusion for 210 minutes
CGP52432, as a GABA B receptor antagonist, reversed the inhibitory effects of GABA B agonists SKF97541 and baclofen on basal and dopamine release.
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