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Augmentation of Tonic GABA(A) Inhibition in Absence Epilepsy: Therapeutic Value of Inverse Agonists at Extrasynaptic GABA(A) Receptors.
Authors: Errington AC, Cope DW, Crunelli V Abstract It is well established that impaired GABAergic inhibition within neuronal networks can lead to hypersynchronous firing patterns that are the typical cellular hallmark of convulsive epileptic seizures. However, recent findings have highlighted that a pathological enhancement of GABAergic signalling within thalamocortical circuits is a necessary and sufficient condition for nonconvulsive typical absence seizure genesis. In particular, increased activation of extrasynaptic GABA(A) receptors (eGABA(A)R) and augmented "tonic" GABA(A) inhibition in thalamocorti...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Oxidative stress in neurodegeneration.
Authors: Shukla V, Mishra SK, Pant HC Abstract It has been demonstrated that oxidative stress has a ubiquitous role in neurodegenerative diseases. Major source of oxidative stress due to reactive oxygen species (ROS) is related to mitochondria as an endogenous source. Although there is ample evidence from tissues of patients with neurodegenerative disorders of morphological, biochemical, and molecular abnormalities in mitochondria, it is still not very clear whether the oxidative stress itself contributes to the onset of neurodegeneration or it is part of the neurodegenerative process as secondary manifest...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Dysregulation of iron metabolism in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.
Authors: Oshiro S, Morioka MS, Kikuchi M Abstract Dysregulation of iron metabolism has been observed in patients with neurodegenerative diseases (NDs). Utilization of several importers and exporters for iron transport in brain cells helps maintain iron homeostasis. Dysregulation of iron homeostasis leads to the production of neurotoxic substances and reactive oxygen species, resulting in iron-induced oxidative stress. In Alzheimer's disease (AD) and Parkinson's disease (PD), circumstantial evidence has shown that dysregulation of brain iron homeostasis leads to abnormal iron accumulation. Several genetic s...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Chronic Treatment with a Promnesiant GABA-A α5-Selective Inverse Agonist Increases Immediate Early Genes Expression during Memory Processing in Mice and Rectifies Their Expression Levels in a Down Syndrome Mouse Model.
Authors: Braudeau J, Dauphinot L, Duchon A, Loistron A, Dodd RH, Hérault Y, Delatour B, Potier MC Abstract Decrease of GABAergic transmission has been proposed to improve memory functions. Indeed, inverse agonists selective for α5 GABA-A-benzodiazepine receptors (α5IA) have promnesiant activity. Interestingly, we have recently shown that α5IA can rescue cognitive deficits in Ts65Dn mice, a Down syndrome mouse model with altered GABAergic transmission. Here, we studied the impact of chronic treatment with α5IA on gene expression in the hippocampus of Ts65Dn and control euploid mice after being trained ...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

The role of uridine adenosine tetraphosphate in the vascular system.
Authors: Matsumoto T, Tostes RC, Webb RC Abstract The endothelium plays a pivotal role in vascular homeostasis, and endothelial dysfunction is a major feature of cardiovascular diseases, such as arterial hypertension, atherosclerosis, and diabetes. Recently, uridine adenosine tetraphosphate (Up(4)A) has been identified as a novel and potent endothelium-derived contracting factor (EDCF). Up(4)A structurally contains both purine and pyrimidine moieties, which activate purinergic receptors. There is an accumulating body of evidence to show that Up(4)A modulates vascular function by actions on endothelial and ...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Neurosteroid Binding Sites on the GABA(A) Receptor Complex as Novel Targets for Therapeutics to Reduce Alcohol Abuse and Dependence.
Authors: Hulin MW, Amato RJ, Porter JR, Filipeanu CM, Winsauer PJ Abstract Despite the prevalence of alcohol abuse and dependence in the US and Europe, there are only five approved pharmacotherapies for alcohol dependence. Moreover, these pharmacotherapeutic options have limited clinical utility. The purpose of this paper is to present pertinent literature suggesting that both alcohol and the neurosteroids interact at the GABA(A) receptor complex and that the neurosteroid sites on this receptor complex could serve as new targets for the development of novel therapeutics for alcohol abuse. This paper will a...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Anti-Inflammatory Activity of Delonix regia (Boj. Ex. Hook).
Authors: Shewale VD, Deshmukh TA, Patil LS, Patil VR Abstract The present work was to evaluate the anti-inflammatory activity of Delonix regia leaves (Family: Caesalpiniaceae). The powder of Delonix regia leaves was subjected to extraction with ethanol in soxhlet extractor. The ethanol extract after preliminary phytochemical investigation showed the presence of sterols, triterpenoids, phenolic compounds and flavonoids. The anti-inflammatory activity was studied using carrageenan-induced rat paw edema and cotton pellet granuloma at a three different doses (100, 200, and 400 mg/kg b.w. p.o.) of ethanol ext...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Central and Peripheral GABA(A) Receptor Regulation of the Heart Rate Depends on the Conscious State of the Animal.
In conclusion, the impact of changes in GABAergic input is very difficult to predict in these settings, emphasizing the need for experiments performed in conscious animals when aiming at determining the cardiovascular effects of compounds acting on GABAergic neurons. PMID: 22162673 [PubMed] (Source: Advances in Pharmacological Sciences)
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

A Comparison of the α2/3/5 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain.
In this study, we have investigated the effects of the medium-efficacy positive allosteric modulator (PAM) L-838,417 and the low-efficacy PAM TPA023 in a number of preclinical inflammatory and neuropathic pain models. We conclude that either the higher level of efficacy at α2/3 or efficacy at α5 is required for compounds to have a significant analgesic effect in a range of models, and, therefore, although the side-effect profile of compounds can be reduced compared to typical benzodiazepines, it is unlikely that it can be completely eliminated. PMID: 22162674 [PubMed] (Source: Advances in Pharmacological Sciences)
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Effects of grape seed extract, vitamin C, and vitamin e on ethanol- and aspirin-induced ulcers.
Authors: Cuevas VM, Calzado YR, Guerra YP, Yera AO, Despaigne SJ, Ferreiro RM, Quintana DC Abstract Effects of GSE and vitamins C and E on aspirin- and ethanol-induced gastric ulcer and associated increases of lipid peroxidation in rats were compared. Two experiments were conducted. Rats were randomized into eight groups: a negative control and seven groups that received aspirin or ethanol for ulcer induction: one positive control (vehicle) and six with VC, VE, or GSE (25 and 250 mg/kg). Ulcer indexes and gastric levels of malondialdehyde (MDA) were quantified. VC, VE, and GSE (25 and 250 mg/kg) decrea...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

The anti-inflammatory role of vitamin e in prevention of osteoporosis.
Authors: Nazrun AS, Norazlina M, Norliza M, Nirwana SI Abstract There is growing evidence that inflammation may be one of the causal factors of osteoporosis. Several cytokines such as IL-1, IL-6, RANKL, OPG, and M-CSF were implicated in the pathogenesis of osteoporosis. These cytokines are important determinants of osteoclast differentiation and its bone resorptive activity. Anticytokine therapy using cytokine antagonists such as IL-receptor antagonist and TNF-binding protein was able to suppress the activity of the respective cytokines and prevent bone loss. Several animal studies have shown that vitamin ...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Sedative and Hypnotic Activities of the Methanolic and Aqueous Extracts of Lavandula officinalis from Morocco.
In conclusion, these results suggest that the methanolic and aqueous extracts of Lavandula officinalis possess potent sedative and hypnotic activities, which supported its therapeutic use for insomnia. PMID: 22162677 [PubMed] (Source: Advances in Pharmacological Sciences)
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Antinociceptive and Anti-Inflammatory Activities of Leaf Methanol Extract of Cotyledon orbiculata L. (Crassulaceae).
Authors: Amabeoku GJ, Kabatende J Abstract Leaf methanol extract of C. orbiculata L. was investigated for antinociceptive and anti-inflammatory activities using acetic acid writhing and hot-plate tests and carrageenan-induced oedema test in mice and rats, respectively. C. orbiculata (100-400 mg/kg, i.p.) significantly inhibited acetic acid-induced writhing and significantly delayed the reaction time of mice to the hot-plate-induced thermal stimulation. Paracetamol (300 mg/kg, i.p.) significantly inhibited the acetic acid-induced writhing in mice. Morphine (10 mg/kg, i.p.) significantly delayed the re...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Supplementation of vitamin C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: a randomized, double-blind study.
In conclusion, oral supplementation of vitamin C with metformin reverses ascorbic acid levels, reduces FBS, PMBG, and improves HbA1c. Hence, both the drugs in combination may be used in the treatment of type 2 DM to maintain good glycemic control. PMID: 22242019 [PubMed] (Source: Advances in Pharmacological Sciences)
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research

Effect of a CNS-Sensitive Anticholinesterase Methane Sulfonyl Fluoride on Hippocampal Acetylcholine Release in Freely Moving Rats.
Authors: Imanishi T, Hossain MM, Suzuki T, Xu P, Sato I, Kobayashi H Abstract Anticholinesterases (antiChEs) are used to treat Alzheimer's disease. The comparative effects of two antiChEs, methanesulfonyl fluoride (MSF) and donepezil, on the extracellular levels of ACh in the hippocampus were investigated by in vivo microdialysis in freely moving rats. MSF at 1 and 2 mg/kg produced a dose-dependent increase in ACh efflux from 10 min to at least 3 hrs after injection. At 2 mg/kg, the increase was still present at 24 hr. Donepezil at 1 mg/kg showed a similar but smaller effect, and, paradoxically...
Source: Advances in Pharmacological Sciences - November 25, 2014 Category: Drugs & Pharmacology Tags: Adv Pharmacol Sci Source Type: research