The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. (wikimili.com)
However, borneol-induced inward currents were partially decreased in the presence of picrotoxin, a γ-aminobutyric acid (GABA) A receptor antagonist, or strychnine, a glycine receptor antagonist, and was almost suppressed in the presence of picrotoxin and strychnine. (kjpp.net)
Antagonist2
Bicuculline is a phthalide-isoquinoline compound that is a light-sensitive competitive antagonist of GABAA receptors. (wikipedia.org)
citation needed] In addition to being a potent GABAA receptor antagonist, bicuculline can be used to block Ca2+-activated potassium channels. (wikipedia.org)
Inhibitory2
The action of bicuculline is primarily on the ionotropic GABAA receptors, which are ligand-gated ion channels concerned chiefly with the passing of chloride ions across the cell membrane, thus promoting an inhibitory influence on the target neuron. (wikipedia.org)
The half-maximal inhibitory concentration (IC50) of bicuculline on GABAA receptors is 3 μM. (wikipedia.org)
Structure2
Sensitivity to bicuculline is defined by IUPHAR as a major criterion in the definition of GABAA receptors Picrotoxin Hydrastine (very similar in structure) Johnston, Graham AR (2013). (wikipedia.org)
The compound structure was established in 1926, when it was found to be identical with that of prunetol . (wikipedia.org)
Competitive antagonist1
Bicuculline is a phthalide-isoquinoline compound that is a light-sensitive competitive antagonist of GABAA receptors. (wikipedia.org)
The action of bicuculline is primarily on the ionotropic GABAA receptors, which are ligand-gated ion channels concerned chiefly with the passing of chloride ions across the cell membrane, thus promoting an inhibitory influence on the target neuron. (wikipedia.org)
Clonic seizures2
Both compounds also significantly prevented clonic seizures, tonic seizures, and lethality induced by pentylenetetrazol in mice when given orally. (bvsalud.org)
Tiagabine has little efficacy against maximal electroshock seizures in rats and is only partially effective against subcutaneous PTZ-induced clonic seizures in mice, picrotoxin-induced tonic seizures in the mouse, bicuculline-induced seizures in the rat, and photic seizures in photosensitive baboons. (nih.gov)
Subcutaneous1
Whether those compounds that are effective in other ETSP screens are also found to elevate seizure threshold in the subcutaneous bicuculline and picrotoxin tests may provide therapeutic efficacy in the clinical management of epilepsy but will necessarily have to await the results of any ongoing or planned clinical trials in the patient with epilepsy. (nih.gov)
Receptors4
The half-maximal inhibitory concentration (IC50) of bicuculline on GABAA receptors is 3 μM. (wikipedia.org)
Sensitivity to bicuculline is defined by IUPHAR as a major criterion in the definition of GABAA receptors Picrotoxin Hydrastine (very similar in structure) Johnston, Graham AR (2013). (wikipedia.org)
Additionally, picrotoxin acts on GABAA receptors through a noncompetitive antagonism of the chloride channel, stabilizing the GABAA receptor-coupled Cl-channel in a non-conducting state and thus reducing GABAergic inhibitory tone [3]. (nih.gov)
Finally, at receptors containing α1β2(Y157S)γ2L subunits, both bicuculline and gabazine showed weak agonist activity and actually potentiated responses to alphaxalone. (jneurosci.org)
GABAA2
citation needed] In addition to being a potent GABAA receptor antagonist, bicuculline can be used to block Ca2+-activated potassium channels. (wikipedia.org)
Met), the ETSP employs additional chemoconvulsant tests wherein a seizure is induced by the GABAA antagonist, bicuculline, and the GABAA chloride-channel blocker, picrotoxin. (nih.gov)
Blocker1
An apparent resting state, determined first in the absence of modulators, was recapitulated with the specific inhibitor (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid and blocker picrotoxin and provided a rationale for bicuculline insensitivity. (biophysics.se)
Seizures2
In the present study, both compounds significantly prevented seizures in mice induced by 6 Hz (44 mA) electrical stimulation without significantly altering motoric function on a rotarod after intraperitoneal administration. (bvsalud.org)
Oral administration of each compound produced dose-dependent increases in the latency for both clonic and tonic seizures and the lethality induced by pentylenetetrazol (PTZ) in mice. (bvsalud.org)
Convulsant1
The commonly used antiepileptic drugs carbamazepine, phenytoin, valproate, phenobarbital and clonazepam, as well as the convulsant agent t-butylbicyclophosphorothionate (TBPS), picrotoxin and bicuculline did not displace [3H]levetiracetam binding. (nih.gov)
Excitatory1
This compound is also routinely used to isolate glutamatergic (excitatory amino acid) receptor function. (wikipedia.org)
Anticonvulsant4
These results support a possible role of this binding site in the anticonvulsant activity of levetiracetam and substantiate the singular pharmacological profile of this compound. (nih.gov)
i.e., the s.c. bicuculline (BIC) or s.c. picrotoxin (PIC) tests that can be used for evaluating the anticonvulsant potential of investigational ASD s. (nih.gov)
Thus, the ETSP utilizes a battery of tests to characterize the anticonvulsant potential of an investigational compound. (nih.gov)
The anticonvulsant screening process involves researchers from academia and industry in the U.S. and abroad ("ASP participants") submitting compounds to the ASP for tests of anticonvulsant efficacy in a series of animal (rodent) seizure models. (nih.gov)
Convulsions3
The effect on picrotoxin-induced convulsions was tested in rats pretreated with 5 mg/kg i.p. baclofen (Lioresal, ClBA-Geigy) and 1 hr later with 6 mg/kg s.c. picrotoxin (Fluke). (erowid.org)
Picrotoxin (2 mg/kg) stimulated this reflex which occasionally was accompanied by convulsions. (erowid.org)
Baclofen did not protect either intact nor spinal rats against picrotoxin-induced convulsions. (erowid.org)
Recently, compounds which bind avidly to benzodiazepine binding sites have been shown to possess diazepam antagonist properties. (nih.gov)
Dose2
The high dose of baclofen (5 mg/kg) completely antagonized the stimulatory action of picrotoxin abolishing the flexor reflex and prevented the stimulation induced by this compound. (erowid.org)
The test compound is given at or below the TD50 dose determined in Test 4 and tested at the s.c. (nih.gov)
Clinical1
At present, no single ETSP screen can solely predict the clinical potential of an investigational compound. (nih.gov)
Molecular1
Compound design was guided by molecular docking using the available crystal structure of the α1ß3γ2 GABAAR and correlated with in vitro binding data. (bvsalud.org)
Effects1
Further discussion helped clarify that the working group's general position on screening for compounds' effects on comorbidities reflects the current lack of strong animal models for these conditions. (nih.gov)
Activity2
For effective compounds, activity will be quantitated in groups of 8 animals and the ED50 and 95% confidence interval of the test compound will be determined by probit analysis. (nih.gov)
In 1938, Houston Merrit and Tracy Putnam described animal models for screening multiple compounds for antiepileptic activity in the Journal of the American Medical Association. (medscape.com)
Found1
We also examined the actions of blocking drugs and found that neither bicuculline nor gabazine are competitive inhibitors of currents gated by alphaxalone or pentobarbital. (jneurosci.org)
Brain2
The compounds bound to brain GABAARs. (bvsalud.org)
Although all compounds were orally bioavailable, structural changes reduced the plasma and brain (FR-II-60 and KPP-III-51) exposures relative to KRM-II-81. (bvsalud.org)
Lack1
Other compounds including physostigmine, naloxone, bicuculline, picrotoxin, caffeine and theophylline, lack appreciable affinity for benzodiazepine binding sites but do antagonize at least some of the behavioral actions of diazepam. (nih.gov)
Potential1
A deuterated structural analog (D5-KRM-II-81) was made as a potential backup compound and studied here in comparison to KRM-II-81. (bvsalud.org)
Increasing doses of picrotoxin (2, 3 and 4 mg/kg), given in succession to the rat with the reflex abolished by baclofen resulted in occurrence of single twitches preceding the death of animals. (erowid.org)
Models1
Bicuculline and picrotoxin are two widely-used chemoconvulsant models of seizure susceptibility and seizure threshold. (nih.gov)