The GABA-B antagonist CGP 36742 prevent PTZ-kindling-provoked amnesia in rats

Genkova-Papazova, M.; Petkova, B.; Шишкова, Н.; Lazarova-Bakarova, M.

doi:10.1016/s0924-977x(00)00082-1

Cited by 20 publications

(4 citation statements)

References 46 publications

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“…In fact, GABA B receptor antagonist may increase the expression of both neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in rat hippocampus (Heese et al, 2000). Similarly, GABA B receptor agonist failed to inhibit Aβ-induced neuronal death (Lee et al, 2005; Marcade et al, 2008), while GABA B antagonist may improve cognitive performance in several animal models (Farr et al, 2000; Genkova-Papazova et al, 2000). New GABA B receptor antagonists have been developed for numerous in vitro and in vivo studies (Froestl, 2010).…”

Section: Aβ and Gabaergic Neurotransmissionmentioning

confidence: 99%

GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimerâ€™s disease

Nava-Mesa¹,

Jiménez‐Díaz²,

Yajeya³

et al. 2014

Front. Cell. Neurosci.

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline, brain atrophy due to neuronal and synapse loss, and formation of two pathological lesions: extracellular amyloid plaques, composed largely of amyloid-beta peptide (Aβ), and neurofibrillary tangles formed by intracellular aggregates of hyperphosphorylated tau protein. Lesions mainly accumulate in brain regions that modulate cognitive functions such as the hippocampus, septum or amygdala. These brain structures have dense reciprocal glutamatergic, cholinergic, and GABAergic connections and their relationships directly affect learning and memory processes, so they have been proposed as highly susceptible regions to suffer damage by Aβ during AD course. Last findings support the emerging concept that soluble Aβ peptides, inducing an initial stage of synaptic dysfunction which probably starts 20–30 years before the clinical onset of AD, can perturb the excitatory–inhibitory balance of neural circuitries. In turn, neurotransmission imbalance will result in altered network activity that might be responsible of cognitive deficits in AD. Therefore, Aβ interactions on neurotransmission systems in memory-related brain regions such as amygdaloid complex, medial septum or hippocampus are critical in cognitive functions and appear as a pivotal target for drug design to improve learning and dysfunctions that manifest with age. Since treatments based on glutamatergic and cholinergic pharmacology in AD have shown limited success, therapies combining modulators of different neurotransmission systems including recent findings regarding the GABAergic system, emerge as a more useful tool for the treatment, and overall prevention, of this dementia. In this review, focused on inhibitory systems, we will analyze pharmacological strategies to compensate neurotransmission imbalance that might be considered as potential therapeutic interventions in AD.

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Section: Aβ and Gabaergic Neurotransmissionmentioning

confidence: 99%

GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimerâ€™s disease

Nava-Mesa¹,

Jiménez‐Díaz²,

Yajeya³

et al. 2014

Front. Cell. Neurosci.

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“…Functional studies on ρ1 GABA C receptors expressed in oocytes showed however that CGP36742 acted as a GABA C receptor antagonist with a potency approximately half that displayed against GABA B receptors [72]. CGP36742 has shown promising therapeutic potential for the treatment of cognitive deficits [73,74]. As not all orally active GABA B antagonists show this therapeutic potential [71], it is possible that antagonism of GABA C receptors contributes to these effects [66,72].…”

Section: Gaba C Receptor Antagonistsmentioning

confidence: 99%

GABAC Receptors as Drug Targets

Johnston¹,

Chebib²,

Hanrahan³

et al. 2003

CDTCNSND

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GABA(C) receptors are the least studied of the three major classes of GABA receptors. The physiological roles of GABA(C) receptors are still being unravelled and the pharmacology of these receptors is being developed. A range of agents has been described that act on GABA(C) receptors with varying degrees of specificity as agonists, partial agonists, antagonists and allosteric modulators. Pharmacological differences are known to exist between subtypes of cloned GABA(C) receptors that have been cloned from mammalian sources. There is evidence for functional GABA(C) receptors in the retina, spinal cord, superior colliculus, pituitary and gastrointestinal tract. Given the lower abundance and less widespread distribution of GABA(C) receptors in the CNS compared to GABA(A) receptors, GABA(C) receptors may be a more selective drug target than GABA(A) receptors. The major indications for drugs acting on GABA(C) receptors are in the treatment of visual, sleep and cognitive disorders. The most promising leads are THIP, a GABA(C) receptor antagonist in addition to its well known activity as a GABA(A) receptor partial agonist, which is being evaluated for sleep therapy, and CGP36742, an orally active GABA(B) and GABA(C) receptor antagonist, which enhances cognition. Analogues of THIP and CGP36742, such as aza-THIP, that are selective for GABA(C) receptors are being developed. TPMPA and related compounds such as P4MPA, PPA and SEPI are also important leads for the development of systemically active selective GABA(C) receptor antagonists.

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“…PTZ-induced kindling is a well-accepted model to investigate and analyze the pathophysiological mechanisms and behavioral characteristics during epileptogenesis [22]. The symptoms of epileptic seizures induced by PTZ kindling in animal models were found to be clinically relevant and similar to those of human temporal lobe epilepsy [23] and generalized tonic-clonic convulsions [22]. In the present study, administration of PTZ (35 mg/kg) for a period of 21 days (21 injections) in AdeA1R-knockout mice successfully established the epilepsy model.…”

Section: Discussionmentioning

confidence: 99%

Chaihu plus Longgu Muli Decoction Alleviated Brain Injury in Pentylenetetrazole-Kindled Epileptic Mice by Regulating Cyclooxygenase-2/Prostaglandin E2/Multidrug Transporter Pathway

Shan

Zhang

Gou

et al. 2021

BioMed Research International

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Objective. To evaluate the effect of CLMD administration on epileptic seizures and brain injury in pentylenetetrazole- (PZT-) kindled mice. Methods. The effect of pretreatment with CLMD (5, 10, and 20 ml/kg (mg/kg) by gavage) for seven days on PTZ-induced kindling, duration and grade of kindling-induced seizures, and pathological injury in the cortex and hippocampus was evaluated. Male BALB/c mice with adenosine A1 receptor knockout were subjected to intraperitoneal injection of PTZ (35 mg/kg) once every day until kindling was successfully induced. Quantitative reverse transcription polymerase chain reaction, immunofluorescence, and western blot were performed to assess the mRNA and protein levels of p-glycoprotein (PGP), multidrug resistance-associated protein 1 (MRP1), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and adenylate kinase (ADK) in the cortex and hippocampus. Results. PTZ successfully induced kindling in mice after 21 days, wherein CLMD showed an obvious dose-dependent antiepileptic effect. High-dose CLMD significantly increased the latency of epileptic seizures, decreased the sustained time of epileptic seizures and the seizure grade, and ameliorated the histopathological changes in the cortex and hippocampus. Furthermore, PTZ kindling induced significantly higher levels of PGP, MRP1, COX-2, PGE2, and ADK, but this effect was inhibited by pretreatment with CLMD in a dose-dependent manner. Conclusion. Pretreatment with CLMD attenuates PTZ-kindled convulsions and brain injury in mice. The mechanism may be related to the cyclooxygenase-2/prostaglandin E2/multidrug transporter pathway.

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The GABA-B antagonist CGP 36742 prevent PTZ-kindling-provoked amnesia in rats

Cited by 20 publications

References 46 publications

GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimerâ€™s disease

GABAergic neurotransmission and new strategies of neuromodulation to compensate synaptic dysfunction in early stages of Alzheimerâ€™s disease

GABAC Receptors as Drug Targets

Chaihu plus Longgu Muli Decoction Alleviated Brain Injury in Pentylenetetrazole-Kindled Epileptic Mice by Regulating Cyclooxygenase-2/Prostaglandin E2/Multidrug Transporter Pathway

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