Probing the Pharmacophore of Ginkgolides as Glycine Receptor Antagonists

2007 ◽  
Vol 50 (7) ◽  
pp. 1610-1617 ◽  
Author(s):  
Anders A. Jensen ◽  
Nasreen Begum ◽  
Stine B. Vogensen ◽  
Kolja M. Knapp ◽  
Klaus Gundertofte ◽  
...  
Keyword(s):  
Glycine Receptor ◽  
Receptor Antagonists ◽  
Glycine Receptor Antagonists

Effects of strychnine-insensitive glycine receptor antagonists and sigma agents on working memory performance

1992 ◽  
Vol 3 (4) ◽  
pp. 393???402 ◽  
Author(s):  
D. B. Clissold ◽  
E. W. Karbon ◽  
J. W. Ferkany ◽  
T. Hartman ◽  
M. J. Pontecorvo
Keyword(s):  
Working Memory ◽  
Memory Performance ◽  
Glycine Receptor ◽  
Receptor Antagonists ◽  
Glycine Receptor Antagonists

Oxime Ethers of (E)-11-Isonitrosostrychnine as Highly Potent Glycine Receptor Antagonists

2016 ◽  
Vol 79 (12) ◽  
pp. 2997-3005 ◽  
Author(s):  
Amal M. Y. Mohsen ◽  
Yasmine M. Mandour ◽  
Edita Sarukhanyan ◽  
Ulrike Breitinger ◽  
Carmen Villmann ◽  
...  
Keyword(s):  
Glycine Receptor ◽  
Receptor Antagonists ◽  
Glycine Receptor Antagonists

MDL 100,458 and MDL 102,288: two potent and selective glycine receptor antagonists with different functional profiles

1995 ◽  
Vol 284 (1-2) ◽  
pp. 109-118 ◽  
Author(s):  
John H. Kehne ◽  
Bruce M. Baron ◽  
Boyd L. Harrison ◽  
Timothy C. McCloskey ◽  
Michael G. Palfreyman ◽  
...  
Keyword(s):  
Glycine Receptor ◽  
Receptor Antagonists ◽  
Functional Profiles ◽  
Glycine Receptor Antagonists

scholarly journals Effect of glycine and glycine receptor antagonists on NMDA-induced brain injury

1989 ◽  
Vol 107 (1-3) ◽  
pp. 279-283 ◽  
Author(s):  
John E. Uckele ◽  
John W. McDonald ◽  
Michael V. Johnston ◽  
Faye S. Silverstein
Keyword(s):  
Brain Injury ◽  
Glycine Receptor ◽  
Receptor Antagonists ◽  
Glycine Receptor Antagonists

Antagonism of the Antinocifensive Action of Halothane by Intrathecal Administration of GABA-A Receptor Antagonists

1996 ◽  
Vol 84 (5) ◽  
pp. 1205-1214 ◽  
Author(s):  
Peggy Mason ◽  
Casey A. Owens ◽  
Donna L. Hammond
Keyword(s):  
Spinal Cord ◽  
Receptor Antagonist ◽  
Gabaa Receptor ◽  
Glycine Receptor ◽  
Intrathecal Administration ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Receptor Antagonists ◽  
Response Latencies ◽  
Halothane Concentration

Background The hind brain and the spinal cord, regions that contain high concentrations of gamma-aminobutyric acid (GABA) and GABA receptors, have been implicated as sites of action of inhalational anesthetics. Previous studies have established that general anesthetics potentiate the effects of gamma-aminobutyric acid at the GABAA receptor. It was therefore hypothesized that the suppression of nocifensive movements during anesthesia is due to an enhancement of GABAA receptor-mediated transmission within the spinal cord. Methods Rats in which an intrathecal catheter had been implanted 1 week earlier were anesthetized with halothane. Core temperature was maintained at a steady level. After MAC determination, the concentration of halothane was adjusted to that at which the rats last moved in response to tail clamping. Saline, a GABAA, a GABAB, or glycine receptor antagonist was then injected intrathecally. The latency to move in response to application of the tail clamp was redetermined 5 min later, after which the halothane concentration was increased by 0.2%. Response latencies to application of the noxious stimulus were measured at 7-min intervals during the subsequent 35 min. To determine whether these antagonists altered baseline response latencies by themselves, another experiment was conducted in which the concentration of halothane was not increased after intrathecal administration of GABAA receptor antagonists. Results Intrathecal administration of the GABAA receptor antagonists bicuculline (0.3 micrograms) or picrotoxin (0.3, 1.0 micrograms) antagonized the suppression of nocifensive movement produced by the small increase in halothane concentration. In contrast, the antinocifensive effect of the increase in halothane concentration was not attenuated by the GABAB receptor antagonist CGP 35348 or the glycine receptor antagonist strychnine. By themselves, the GABAA receptor antagonists did not alter response latency in rats anesthetized with sub-MAC concentrations of halothane. Conclusions Intrathecal administration of bicuculline or picrotoxin, at doses that do not change the latency to pinch-evoked movement when administered alone, antagonized the suppression of noxious-evoked movement produced by halothane concentrations equal to or greater than MAC. These results suggest that enhancement of GABAA receptor-mediated transmission within the spinal cord contributes to halothane's ability to suppress nocifensive movements.

Synaptic activation of bulbospongiosus motoneurons via dorsal gray commissural inputs

2013 ◽  
Vol 109 (1) ◽  
pp. 58-67 ◽  
Author(s):  
Tyler K. Best ◽  
Lesley Marson ◽  
Karl B. Thor ◽  
Edward C. Burgard
Keyword(s):  
Glutamate Receptor ◽  
Glycine Receptor ◽  
Reversal Potential ◽  
Membrane Resistance ◽  
Ventral Horn ◽  
Receptor Antagonists ◽  
Postsynaptic Potentials ◽  
Glutamate Receptor Antagonists ◽  
Excitatory Responses ◽  
Slow Depolarization

Ejaculation is controlled by coordinated and rhythmic contractions of bulbospongiosus (BSM) and ischiocavernosus muscles. Motoneurons that innervate and control BSM contractions are located in the dorsomedial portion of the ventral horn in the L5–6 spinal cord termed the dorsomedial (DM) nucleus. We characterized intrinsic properties of DM motoneurons as well as synaptic inputs from the dorsal gray commissure (DGC). Electrical stimulation of DGC fibers elicited fast inhibitory and excitatory responses. In the presence of glutamate receptor antagonists, both fast GABAergic as well as glycinergic inhibitory postsynaptic potentials (IPSPs) were recorded. No slow GABAB-mediated inhibition was evident. In the presence of GABAA and glycine receptor antagonists, DGC stimulation elicited fast glutamatergic excitatory responses that were blocked by application of CNQX. Importantly, a slow depolarization (timescale of seconds) was routinely observed that sufficiently depolarized the DM motoneurons to fire “bursts” of action potentials. This slow depolarization was elicited by a range of stimulus train frequencies and was insensitive to glutamate receptor antagonists (CNQX and d-APV). The slow depolarization was accompanied by an increase in membrane resistance with an extrapolated reversal potential near the K+ Nernst potential. It was mediated by the combination of the block of a depolarization-activated K+ current and the activation of a QX-314-sensitive cation current. These results demonstrate that fast synaptic responses in DM motoneurons are mediated primarily by glutamate, GABA, and glycine receptors. In addition, slow nonglutamatergic excitatory postsynaptic potentials (EPSPs), generated through DGC stimulation, can elicit burstlike responses in these neurons.

Effects of GABA Receptor Antagonists on Retinal Glycine Receptors and on Homomeric Glycine Receptor Alpha Subunits

2005 ◽  
Vol 93 (6) ◽  
pp. 3120-3126 ◽  
Author(s):  
Peiyuan Wang ◽  
Malcolm M. Slaughter
Keyword(s):  
Gaba Receptor ◽  
Ganglion Cells ◽  
Glycine Receptor ◽  
Hek293 Cells ◽  
Receptor Subtypes ◽  
Glycine Receptors ◽  
Receptor Antagonists ◽  
Gaba Antagonists ◽  
Human Embryonic Kidney Cells ◽  
Competitive Inhibitors

Glycinergic and GABAergic inhibition are juxtaposed at one retinal synaptic layer yet likely perform different functions. These functions have usually been evaluated using receptor antagonists. In examining retinal glycine receptors, we were surprised to find that commonly used concentrations of GABA antagonists blocked significant fractions of the glycine current. In retinal amacrine and ganglion cells, the competitive GABAA receptor antagonists (bicuculline and SR95531) were also competitive GlyR antagonists. Picrotoxinin produced a noncompetitive inhibition of retinal GlyRs. [1,2,5,6-tetrahydropyridine-4-yl] methylphosphinic acid, the GABACR antagonist, did not inhibit glycine receptors. All three GABAA receptor antagonists were competitive inhibitors of homomeric α1 or α2 GlyRs expressed in human embryonic kidney cells (HEK293) cells. Interestingly, bicuculline was much more effective at α2 GlyRs and might be used to separate glycine receptor subtypes. Thus commonly used concentrations of GABA antagonists do not unambiguously differentiate GABA and glycine pathways. Picrotoxinin inhibition of GABAC receptors requires two amino acids in the second transmembrane region (TM2): 2′ serine and 6′ threonine. Although TM2 regions in GABA and glycine receptors are highly homologous, neither 2′ serine nor 6′ threonine is essential for picrotoxinin sensitivity in glycine receptors.

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