GABA Antagonists

Publication Title: 
BMJ clinical evidence

INTRODUCTION: Dystonia is usually a lifelong condition with persistent pain and disability. Focal dystonia affects a single part of the body; generalised dystonia can affect most or all of the body. It is more common in women, and some types of dystonia are more common in people of European Ashkenazi Jewish descent. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments, surgical treatments, and physical treatments for focal, and for generalised dystonia?

Author(s): 
Snaith, Ailsa
Wade, Derick
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

GABA(A) receptors have been implicated in mediating several acute effects of ethanol including anxiolysis, ataxia, sedation/hypnosis, and anticonvulsant activity. Ethanol sensitivity of neurons has been associated with expression of alpha1 subunit-containing receptors. The objective of this study was to determine the contribution of alpha1 subunit containing receptors to ethanol responses in comparison to neurosteroids and other anesthetics using GABA(A) receptor alpha1 subunit knockout mice.

Author(s): 
Kralic, J. E.
Wheeler, M.
Renzi, K.
Ferguson, C.
O'Buckley, T. K.
Grobin, A. C.
Morrow, A. L.
Homanics, G. E.
Publication Title: 
Neuropharmacology

We studied the effects of pentobarbital and antagonists of glutamate, gamma-aminobutyrate (GABA), and glycine receptors on extracellular activity in ventrobasal thalamic slices. Pentobarbital at sedative-hypnotic concentration (20 microM) reversibly induced 1-15 Hz oscillations. Sustained oscillations required electrical stimulation of internal capsule, but not elevated temperature or low [Mg2+]. Anesthetic concentration (200 microM) of pentobarbital evoked only transient oscillations. Kynurenate-sensitive glutamate receptors were essential for oscillations.

Author(s): 
Ran, I.
Mathers, D. A.
Puil, E.
Publication Title: 
Journal of Pharmacological Sciences

The endogenous brain constituent, gamma-hydroxybutyric acid (GHB), as well as its prodrug, gamma-butyrolactone (GBL), have recently gained interest in the drug addiction field due to their abuse potential and fatalities caused by overdose. It is known that GHB has two sites of actions: the gamma-aminobutyric acid(B) (GABA(B)) receptor and a specific-GHB binding site. The present study was designed to extend to GBL the investigations on the contribution of the GABA(B) receptor and the specific-GHB binding site to its in vivo effects.

Author(s): 
Carai, Mauro A. M.
Lobina, Carla
Maccioni, Paola
Cabras, Claudia
Colombo, Giancarlo
Gessa, Gian Luigi
Publication Title: 
Anesthesiology

BACKGROUND: It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. METHODS: Experiments were conducted in rats where the loss of righting reflex (LORR) was used as a marker of the hypnotic state.

Author(s): 
Nguyen, Hai T.
Li, Ke-yong
daGraca, Ralph L.
Delphin, Ellise
Xiong, Ming
Ye, Jiang H.
Publication Title: 
Brain Research

Strychnine-sensitive glycine receptors (GlyR) play a major role in the excitability of CNS neurons and are also a major target of many drugs including some general anesthetics and ethanol. The prefrontal cortex (PFC) is an important substrate responsible for cognitive function and for sedation, as well as hypnosis (unconsciousness) which is induced by general anesthetics and ethanol. However, the functions and the physiological and pharmacological properties of GlyRs in mature PFC neurons have not been well studied.

Author(s): 
Lu, Yongli
Ye, Jiang-Hong
Publication Title: 
Pain

Joint manipulation has long been used for pain relief. However, the underlying mechanisms for manipulation-related pain relief remain largely unexplored. The purpose of the current study was to determine which spinal neurotransmitter receptors mediate manipulation-induced antihyperalgesia. Rats were injected with capsaicin (50 microl, 0.2%) into one ankle joint and mechanical withdrawal threshold measured before and after injection. The mechanical withdrawal threshold decreases 2 h after capsaicin injection.

Author(s): 
Skyba, D. A.
Radhakrishnan, R.
Rohlwing, J. J.
Wright, A.
Sluka, K. A.
Publication Title: 
Brain Research

Bilobalide, a constituent of Ginkgo biloba, has neuroprotective properties. Its mechanism of action is unknown but it was recently found to block GABA(A) receptors. The goal of this study was to test the potential role of a GABAergic mechanism for the neuroprotective activity of bilobalide. In rat hippocampal slices exposed to NMDA, release of choline indicates breakdown of membrane phospholipids. NMDA-induced choline release was almost completely blocked in the presence of bilobalide (10 microM) and under low-chloride conditions.

Author(s): 
Kiewert, Cornelia
Kumar, Vikas
Hildmann, Oksana
Rueda, Misty
Hartmann, Joachim
Naik, Runa S.
Klein, Jochen
Publication Title: 
Brain Research

Labetalol, a combined alpha1, beta1, and beta2 adrenoceptor-blocking drug, has been shown to have analgesic properties in vivo. To determine the underlying mechanisms, we examined its effects on GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous firings of rat ventrolateral periaqueductal gray (PAG) neurons, either mechanically dissociated, or in acute brain slices. These PAG neurons mediate opioid-mediated analgesia and pain transmission and are under tonic control of GABAergic interneurons.

Author(s): 
Xiao, Cheng
Zhou, Chunyi
Atlas, Glen
Delphin, Ellise
Ye, Jiang Hong
Publication Title: 
Anesthesiology

BACKGROUND: It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. METHODS: Experiments were conducted in rats where the loss of righting reflex (LORR) was used as a marker of the hypnotic state.

Author(s): 
Nguyen, Hai T.
Li, Ke-yong
daGraca, Ralph L.
Delphin, Ellise
Xiong, Ming
Ye, Jiang H.

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