To investigate the therapeutic effect of high-dosage gamma-aminobutyric acid (GABA) on acute tetramine (TET) poisoning, 50 Kunming mice were divided into 5 groups at random and the antidotal effects of GABA or sodium dimercaptopropane sulfonate (Na-DMPS) on poisoned mice in different groups were observed in order to compare the therapeutic effects of high-dosage GABA with those of Na-DMPS. Slices of brain tissue of the poisoned mice were made to examine pathological changes of cells. The survival analysis was employed. Our results showed that both high-dosage GABA and Na-DMPS could obviously prolong the survival time, delay onset of convulsion and muscular twitch, and ameliorate the symptoms after acute tetramine poisoning in the mice. Better effects could be achieved with earlier use of high dosage GABA or Na-DMPS. There was no significant difference in prolonging the survival time between high-dose GABA and Na-DMPS used immediately after poisioning. It is concluded that high-dosage GABA can effectively antagonize acute toxicity of teramine in mice. And it is suggested that high-dosage GABA may be used as an excellent antidote for acute TET poisoning in clinical practice. The indications and correct dosage for clinical use awaits to be further studied.
Acute Disease ; Antidotes/*administration & dosage ; Antidotes/therapeutic use ; Bridged Compounds/*poisoning ; Random Allocation ; Rodenticides/*poisoning ; Unithiol/therapeutic use ; gamma-Aminobutyric Acid/*administration & dosage ; gamma-Aminobutyric Acid/therapeutic use

OBJECTIVE: Black sticky rice with giant embryo (BSRGE) contains high GABA content and affects alcohol-related indices among social drinkers, and alcohol intake and anxiety-related behavior of mice. However, it is unknown whether the intake of BSRGE affects GABAergic activity of brain directly. The purpose of this study is to elucidate the effect of oral administration of BSRGE on brain GABA concentrations compared with commercially available GABA compound and regular feeds. METHODS: Twenty-one male C57BL/6 mice were assigned to BSRGE, a regular feed (AIN-76) lacking GABA, and a regular feed containing GABA compound. After feeding freely for 48 h, the cortex and striatum were separated from the brain. An enzyme-linked immunosorbent assay was conducted to measure GABA and glutamate concentrations in mouse brain. RESULTS: The GABA concentration of the BSRGE group was higher than that of regular feed and GABA compound group (p<0.001). However, the GABA compound group showed no significant difference from the regular feed group (p=0.50). CONCLUSION: Intake of BSRGE containing high GABA content increased GABA concentrations in mouse brain compared with regular feed unlike GABA compound. The results of this study constitute an important basis for further investigations into the clinical applications of BSRGE.
Administration, Oral ; Animals ; Brain ; Embryonic Structures ; Enzyme-Linked Immunosorbent Assay ; gamma-Aminobutyric Acid ; Glutamic Acid ; Humans ; Male ; Mice

BACKGROUND: The primary site of action of pregabalin, i.e. the alpha-2-delta subunit of the voltage-dependent calcium channel, is located at the dorsal root ganglion and dorsal horn of the spinal cord. Therefore, the epidural administration of pregabalin could have advantages over oral administration. However, the possibility of its neurotoxicity should be excluded before any attempt at epidural administration. We evaluated the neuronal safety of epidurally-administered pregabalin by observing the sensory/motor changes and examining the histopathology of spinal cord in rats. METHODS: Sixty rats of 180-230 g were divided into three groups; 3 mg of pregabalin dissolved in 0.3 ml saline (group P, n = 20), 0.3 ml 40% alcohol (group A, n = 20), or 0.3 ml normal saline (group N, n = 20) was administered epidurally to the rats in each group. Pinch-toe test, motor function evaluation, and histopathologic examination of vacuolation, chromatolysis, meningeal inflammation, and neuritis were performed at the 1st, 3rd, 7th, and 21st day after each epidural administration. RESULTS: All rats enrolled in group P, like those in group N, showed neither sensory/motor dysfunction nor any histopathological abnormality over the 3-week observation period. In contrast, in group A, 80% of the rats showed abnormal response to the pinch-toe test and all rats showed decreased motor function during the entire evaluation period. In addition, all histopathologic findings of neurotoxicity were observed exclusively in group A. CONCLUSIONS: The epidurally administered pregabalin (about 15 mg/kg) did not cause any neurotoxic evidence, in terms of both sensory/motor function evaluation and histopathological examination in rats.
Administration, Oral ; Animals ; Calcium Channels ; gamma-Aminobutyric Acid ; Ganglia, Spinal ; Horns ; Inflammation ; Injections, Epidural ; Neuritis ; Neurons ; Rats ; Spinal Cord ; Pregabalin

BACKGROUND: Gabapentin is a safe and well-tolerated anticonvulsant with a wide therapeutic index, and it is used for neuropathic pain. The aim of this study was to compare previous dosing methods with the administration of four different doses of gabapentin while maintaining the same maximum daily dose for the safe administration of high doses of the medication. METHODS: The subjects were outpatients with various neuropathic pain syndromes, with at least two of the following symptoms: allodynia, burning pain, shooting pain, or hyperalgesia. The TID group received equal doses of gabapentin 3 times per day, while the QID group received 4 different doses of gabapentin per day. The pain score, frequency of breakthrough pain (BTP), severity and the duration of pain, sleep disturbance due to nocturnal pain, and adverse effects were recorded each day. RESULTS: The average daily pain score and sleep disturbance were significantly reduced in the QID group between days 3 and 10 of the experiment. The adverse effects of the medication were also reduced in the QID group. However, the frequency of BTP and severity and duration of pain were not significantly different between two groups. CONCLUSIONS: Administration of 4 different doses of gabapentin during the initial titration in outpatients with neuropathic pain resulted in a significant reduction in awakening from breakthrough pain and a reduction in the adverse effects of the medication.
Ambulatory Care ; Amines ; Breakthrough Pain ; Burns ; Cyclohexanecarboxylic Acids ; Drug Administration Schedule ; gamma-Aminobutyric Acid ; Humans ; Hyperalgesia ; Neuralgia ; Outpatients

BACKGROUND: Baclofen is a gamma-aminobutyric acid B-receptor agonist, which is usually used for patients with spasticity or patients with nerve injury inducing both spasticity and neuropathic pain. Both oral administration and intrathecal injection via a continuous infusion pump are common treatment methods. The aim of this study was to evaluate the effectiveness of a series of three individual injections of intrathecal baclofen for neuropathic pain without spasticity. METHODS: Thirty-one patients with neuropathic pain were treated with a series of three monthly individual injections of intrathecal baclofen without pump implantation A dose of 50 µg of baclofen was used. 10-cm visual analog scale (VAS) scores of spontaneous pain, allodynia, and hyperalgesia were recorded a week after each injection. Vital signs were monitored to detect any hemodynamic changes, and a myelogram was performed to detect any undesirable cerebrospinal fluid leakage. All patients were hospitalized for at least one day following each injection for close observation and to control any adverse effects. RESULTS: VAS scores of spontaneous pain, allodynia, and hyperalgesia decreased significantly (P < 0.001). The major complications were general weakness, sleepiness, and urinary retention; most of these resolved within one day without any further serious symptoms. CONCLUSIONS: A series of three individual intrathecal baclofen injections was effective for those patients who suffered from neuropathic pain without spasticity or dystonia; no serious complications were observed. However, the average satisfaction score recorded for spontaneous pain was lower than those for allodynia and hyperalgesia.
Administration, Oral ; Baclofen* ; Cerebrospinal Fluid Leak ; Dystonia ; gamma-Aminobutyric Acid ; Hemodynamics ; Humans ; Hyperalgesia ; Infusion Pumps ; Injections, Spinal ; Muscle Spasticity ; Neuralgia* ; Urinary Retention ; Visual Analog Scale ; Vital Signs

BACKGROUND: Pregabalin is an antiepileptic drug that is effective for treating postoperative pain, neuropathic pain, anxiety, and hemodynamic instability. The aim of this study was to investigate the effect of a single preoperative dose of pregabalin in patients with opioid-induced hyperalgesia (OIH). METHODS: Ninety ASA I-II patients undergoing laparoendoscopic single-site urologic surgery were randomly assigned to one of the following three groups that received either pregabalin or placebo 1 h before anesthesia and an intraoperative remifentanil infusion. Group plL received placebo and 0.05 microgram/kg/min remifentanil, group plH received placebo and 0.3 microgram/kg/min remifentanil, and group prH received 300 mg pregabalin plus 0.3 microgram/kg/min remifentanil. The primary endpoint was pain intensity upon movement 1, 6, 12, and 24 h after surgery. Secondary endpoints were the area of hyperalgesia and mechanical hyperalgesia threshold 24 h after surgery, time to first postoperative analgesic requirement, and cumulative postoperative volume of morphine administered via a patient-controlled analgesia (PCA) pump over 24 h. RESULTS: The time to first postoperative analgesic requirement in group plH was significantly shorter than that in group plL. The injected PCA volume was significantly greater in group plH than that in the other two groups. Postoperative pain intensity in group plH was significantly greater than that in the other two groups at 6, 12, and 24 h after surgery. The mechanical hyperalgesia threshold and the area of hyperalgesia around the surgical incision 24 h after surgery in group plH differed significantly from those in the other two groups, which were not significantly different. Adverse effects were comparable among groups. CONCLUSIONS: High-dose remifentanil induced hyperalgesia, including increased pain intensity, increased area of hyperalgesia, and decreased mechanical hyperalgesia threshold. These effects were attenuated by oral administration of a single preoperative dose of pregabalin (300 mg) in patients undergoing laparo-endoscopic single-site urologic surgery.
Administration, Oral ; Analgesia, Patient-Controlled ; Anesthesia ; Anxiety ; gamma-Aminobutyric Acid ; Hemodynamics ; Humans ; Hyperalgesia ; Morphine ; Neuralgia ; Pain, Postoperative ; Passive Cutaneous Anaphylaxis ; Piperidines ; Pregabalin

This study was performed to investigate the sedative-hypnotic activity of gamma-aminobutyric acid (GABA)-enriched fermented marine organisms (FMO), including sea tangle (FST) and oyster (FO) by Lactobacillus brevis BJ20 (L. brevis BJ20). FST and FO were tested for their binding activity of the GABA(A)-benzodiazepine and 5-HT(2C) receptors, which are well-known molecular targets for sleep aids. We also measured the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of FST and FO. In GABA(A) and 5-HT(2C) receptor binding assays, FST displayed an effective concentration-dependent binding affinity to GABA(A) receptor, similar to the binding affinity to 5-HT(2C) receptor. FO exhibited higher affinity to 5-HT(2C) receptor, compared with the GABA(A) receptor. The oral administration of FST and FO produced a dose-dependent decrease in sleep latency and increase in sleep duration in pentobarbital-induced hypnosis. The data demonstrate that FST and FO possess sedative-hypnotic activity possibly by modulating GABA(A) and 5-HT(2C) receptors. We propose that FST and FO might be effective agents for treatment of insomnia.
Administration, Oral ; Animals ; Aquatic Organisms* ; gamma-Aminobutyric Acid ; Hypnosis ; Lactobacillus brevis ; Mice ; Ostreidae ; Receptor, Serotonin, 5-HT2C ; Receptors, GABA-A ; Sleep Initiation and Maintenance Disorders

This study was investigated to know whether pachymic acid (PA), one of the predominant triterpenoids in Poria cocos (Hoelen) has the sedative-hypnotic effects, and underlying mechanisms are mediated via gamma-aminobutyric acid (GABA)-ergic systems. Oral administration of PA markedly suppressed locomotion activity in mice. This compound also prolonged sleeping time, and reduced sleep latency showing synergic effects with muscimol (0.2 mg/kg) in shortening sleep onset and enhancing sleep time induced by pentobarbital, both at the hypnotic (40 mg/kg) and sub-hypnotic (28 mg/kg) doses. Additionally, PA elevated intracellular chloride levels in hypothalamic primary cultured neuronal cells of rats. Moreover, Western blotting quantitative results showed that PA increased the amount of protein level expression of GAD65/67 over a broader range of doses. PA increased alpha- and beta-subunits protein levels, but decreased gamma-subunit protein levels in GABA(A) receptors. The present experiment provides evidence for the hypnotic effects as PA enhanced pentobarbital-induced sleeping behaviors via GABA(A)-ergic mechanisms in rodents. Taken together, it is proposed that PA may be useful for the treatment of sleep disturbed subjects with insomnia.
Administration, Oral ; Animals ; Blotting, Western ; Cocos ; gamma-Aminobutyric Acid ; Hypnotics and Sedatives ; Locomotion ; Mice* ; Muscimol ; Neurons ; Pentobarbital ; Poria ; Rats ; Receptors, GABA-A ; Rodentia ; Sleep Initiation and Maintenance Disorders

OBJECTIVETo research the content changes of excitatory neurotransmitter and inhibitory neurotransmitter in corpus striatum of rats after single-used borneol and combining it with diazepam in hope of comprehending the activity of borneol on central nervous system and to observe whether borneol could increase the penetration of other drugs into the brain.

METHODThe content of four amino acids neurotransmitters in corpus striatum of rats were sampled by brain microdialysis technology at different time after administration and were determined by RP-HPLC which involved pre-column derivation with orthophthaladehyde (OPA), using phosphate gradient elution and fluorescence detection to detect the content of excitatory neurotransmitter aspartate (Asp), glutamate (Glu) and inhibitory neurotransmitter glycine (Gly), gamma-aminobutyric acid (GABA) in standards and samples and carry on statistical analysis.

RESULTThe content of both Gly and GABA in corpus striatum of rats with borneol increased significantly, compared with diazepam group (P < 0.05), while Asp and Glu showed no significant difference.

CONCLUSIONBorneol can improve permeability of diazepam through BBB.

Animals ; Aspartic Acid ; analysis ; Blood-Brain Barrier ; Bornanes ; administration & dosage ; pharmacology ; Corpus Striatum ; chemistry ; drug effects ; Diazepam ; administration & dosage ; pharmacology ; Glutamic Acid ; analysis ; Glycine ; analysis ; Male ; Neurotransmitter Agents ; analysis ; Rats ; Rats, Sprague-Dawley ; gamma-Aminobutyric Acid ; analysis

AIMTo research the spontaneous firing activities during different-frequency stimulation of subthalamic nucleus and microelectrophoresis GABA, Glu and their antagons respectively, approaching the mechanism of DBS in the treatment of Parkinson's disease further.

METHODSUsing extracellular recording to investigate the effect of different-frequency stimulation of STN and microelectrophoresis several drugs on the spontaneous firing activities of the SNr neurons.

RESULTSFor STN stimulation at low frequency, there was no difference on the spontaneous firing activities of SNr neurons between pro-stimulation and meta-stimulation (P > 0.05). With the increasing of stimulation frequency, most of the SNr neurons were inhibited. While during the STN stimulation frequency at high-frequency, the firing rates of inhibited SNr neurons were changed (P < 0.05). Glu had catatonic excitement effect on the SNr neurons, whereas GABA had tonic inhibition effect. 80% of SNr neurons which were inhibited by STN-HFS were not inhibited by STN-HFS on the basis of excitatory effect of BIC.

CONCLUSIONTo treat the motor symptoms of PD, when SIN is selected as the target nucleus, the electrical stimulation with high-frequency should be chosen. It is possible that SIN-HFS modulate the activity of SNr by inhibitory effect of GABA predominantly.

Action Potentials ; physiology ; Animals ; Electric Stimulation ; Electrophoresis ; methods ; Glutamic Acid ; administration & dosage ; pharmacology ; Male ; Neurons ; physiology ; Parkinson Disease ; physiopathology ; therapy ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; physiology ; Subthalamic Nucleus ; physiology ; gamma-Aminobutyric Acid ; administration & dosage ; pharmacology