Phthalideisoquinoline alcaloid norbicuculline have been synthesized by Bischler-Napieralski cyclization. The racemic norbicuculline were resolved into (+) and (-) forms. Methylation of (+ )norbicuculline provided (+)bicuculline. Researching bicucullin synthesis by the method of Bischler – napieralski shows that bicucullin is synthesized from Piperonal and Beta - (3,4 methylendioxy) – phenylethylamin by method of Bischler – napieralski. Isomers of ( ±) erythro and (±) threo norbicucullin are easily separated thank to nhờ sắc kí cột silicagel. Afterwards, optical isomers of (±) norbicucullin are also separated with high optical purity and good output. Methyl changed into (+) erythro norbicucullin is to gather (+) bicucullin gaining standards for biological experiments
Bicuculline ; Pharmaceutical Preparations

PURPOSE: The goal of this study was to investigate the effects of bicuculline(BIC) on the excitability of visual cortex, observe the induction of epileptiform activity and define the characteristics of spontaneous activity. METHODS: We divided 19 to 23-day-old Sprague-Dawley rats into 3 groups by the concentration of BIC:5(n=10), 20(n=12), and 40(n=10) microM. The slices from the rats were incubated in artificial CSF for 1 hour, and then extracellular recordings were performed. RESULTS: Spontaneous epileptiform activities were observed in all of the BIC groups. The latencies of 5, 20, and 40 microM BIC were 31.6+/-13.0, 34.0+/-11.9, and 6.3+/-3.2 min. The frequencies of 5, 20, and 40 microM BIC were 1.1+/-0.5, 2.7+/-1.8, and 19.1+/-23.3 min-1. The amplitudes of 5, 20, and 40 microM BIC were 5.4+/-1.4, 6.9+/-0.9, 11.1+/-1.3 mV. The durations of 5, 20, and 40 microM BIC were 444.6+/-169.1, 865.2+/-151.2, and 1,014.7+/-613.8 ms. CONCLUSION: BIC is associated with increased excitability in the visual cortex and induces spontaneous epileptiform activities. This induction was decreased by D-AP5 or CNQX.
6-Cyano-7-nitroquinoxaline-2,3-dione ; Animals ; Bicuculline* ; Rats ; Rats, Sprague-Dawley ; Visual Cortex

Rat thalamocortical slices maintain synoptic connections between thalamus and cortex. When perfused with low Mg++-ACSF, thalamocortical slices exhibited two main types of spontaneous bursting activity. One is monotonic burst of 3-15 Hz and another is multiphasic bursts which have a tonic burst firing period and a late phase of clonic burst firing. These bursts are similar in frequency and during to EEG recordings from human generalized seizures. Exploiting the advantages of in vitro preparations, the electrophysiological action of taurine were studied. Exogeneous application of taurine profoundly decreased spontaneous bursting activities, which it caused only slight reduction of electrically evoked response in cortical layer. Taurine-induced current was blocked by 40 uM bicuculline, GABA receptor antagonist, in acutely isolated coritcal neurons. These results suggest that endogeneous taurine may regulate the hyperexcitablility through GABAa receptor.
Animals ; Bicuculline ; Electroencephalography ; Fires ; Humans ; Neurons ; Rats* ; Receptors, GABA ; Seizures* ; Taurine* ; Thalamus

Rat thalamocortical slices maintain synoptic connections between thalamus and cortex. When perfused with low Mg++-ACSF, thalamocortical slices exhibited two main types of spontaneous bursting activity. One is monotonic burst of 3-15 Hz and another is multiphasic bursts which have a tonic burst firing period and a late phase of clonic burst firing. These bursts are similar in frequency and during to EEG recordings from human generalized seizures. Exploiting the advantages of in vitro preparations, the electrophysiological action of taurine were studied. Exogeneous application of taurine profoundly decreased spontaneous bursting activities, which it caused only slight reduction of electrically evoked response in cortical layer. Taurine-induced current was blocked by 40 uM bicuculline, GABA receptor antagonist, in acutely isolated coritcal neurons. These results suggest that endogeneous taurine may regulate the hyperexcitablility through GABAa receptor.
Animals ; Bicuculline ; Electroencephalography ; Fires ; Humans ; Neurons ; Rats* ; Receptors, GABA ; Seizures* ; Taurine* ; Thalamus

The aim of this study was to examine the effects of various concentrations of glutamate(10(-8), 10(-6) and 10(-4) M) on the circling movement induced by apomorphine in the unilateral substantia nigra-lesioned rats. Subcutaneous apomorphine(0.1 mg/kg) elicited contralateral circling movement(641.7+/-163.9/hr), Glutamate(10(-6)-10(-4) M) significantly reduced the numbers of apomorphine-induced circling movement. This reducing effect of glutamate was antagonized and/or reversed by 10(-7) M GABA antagonist bicuculline. These results suggest that glutamate reduces circling movement induced by apomorphine and this reducing effect of glutamate may be mediated by increased GABA concentration in striatum and substantia nigra.
Animals ; Apomorphine ; Bicuculline ; Dopamine ; GABA Antagonists ; gamma-Aminobutyric Acid ; Glutamic Acid* ; Rats* ; Substantia Nigra

This study aimed to investigate the existence of GABA receptor and the mechanisms of action of GABA and diazepam of the trachealis muscle isolated from dog. Horizontal muscle strips of 2mm×15mm were prepared from canine trachea, and isometric myography in isolated muscle chamber bubbled with 95/5%-O₂/CO₂ at 36℃, at the pH of 7.4 was performed. Muscle strips contracted responding to the electrical field stimulation (ESP) by 2~20 Hz, 20 msec, monophasic square wave of 60 VDC. GABA and diazepam suppressed the EFS-induced contractions to the similar extent, significantly. (p<0.05). Bicuculline, a GABA(A) receptor antagonist blocked both GABA- and diazepam-inhibitions; but DAVA, a GABA(B) receptor antagoinst did not affect either of them. These results suggest than in the canine trachealis muscle, there may be only GABA(A) receptor, and GABA and diazepam inhibit the contractility via GABA(A) receptor.
Animals ; Bicuculline ; Diazepam ; Dogs ; gamma-Aminobutyric Acid* ; Hydrogen-Ion Concentration ; Myography ; Receptors, GABA ; Receptors, GABA-A ; Trachea

Induced activation of the gamma-aminobutyric acidA (GABA(A)) receptor in the retina of goldfish caused the fish to rotate in the opposite direction to that of the spinning pattern during an optomotor response (OMR) measurement. Muscimol, a GABA(A) receptor agonist, modified OMR in a concentration-dependent manner. The GABA(B) receptor agonist baclofen and GABA(C) receptor agonist CACA did not affect OMR. The observed modifications in OMR included decreased anterograde rotation (0.01~0.03 micrometer), coexistence of retrograde rotation and decreased anterograde rotation (0.1~30 micrometer) and only retrograde rotation (100 micrometer~1 mM). In contrast, the GABA(A) receptor antagonist bicuculline blocked muscimolinduced retrograde rotation. Based on these results, we inferred that the coding inducing retrograde movement of the goldfish retina is essentially associated with the GABA(A) receptor-related visual pathway. Furthermore, from our novel approach using observations of goldfish behavior the induced discrete snapshot duration was approximately 573 ms when the fish were under the influence of muscimol.
Baclofen ; Bicuculline ; Clinical Coding ; Cytarabine ; Goldfish ; Injections, Intraocular ; Muscimol ; Receptors, GABA ; Receptors, GABA-A ; Retina ; Visual Pathways

Experimentally induced cortical disorganization exhibits many anatomical features which are characteristic of cortical malformations in children with early-onset epilepsy. We used an immunocytochemical technique and extracellular field potential recordings from the dorsal hippocampus to determine whether the excitability of the CA1 pyramidal cells was enhanced in rats with experimentally induced hippocampal dysplasia. Compared with control rats, the MAM-treated rats displayed a decrease of paired pulse inhibition. When GABAA receptor antagonists were blocked with 10microM bicuculline, the amplitude of the second population spike of the MAM-treated of rats was similar to that of the first population spike, as was in the control rats. The MAM-treated rats had fewer somatostatin and parvalbumin-immunoreactive neurons than the control rats. These results suggest that the enhanced neuronal responsiveness of the in vivo recording of the CA1 in this animal model may involve a reduction of CA1 inhibition.
Animals ; Bicuculline ; Child ; Epilepsy ; Hippocampus ; Humans ; Models, Animal ; Neurons ; Pyramidal Cells ; Rats* ; Somatostatin

Single unit responses of the ventral posterior medial (VPM) thalamic neurons to stimulation were monitored in anesthetized rats during activation of contralateral primary somatosensory (SI) cortex by GABA antagonist. The temporal changes of afferent sensory transmission were quantitatively analyzed by poststimulus time histogram (PSTH). Mainly, afferent sensory transmission to VPM thalamus was facilitated (15 neurons of total 23) by GABA antagonist (bicuculline) applied to contralateral cortex, while 7 neurons were suppressed. However, when ipsilateral cortex was inactivated by GABA agonist, musimol, there was significant suppression of afferent sensory transmission of VPM thalamus. This suppressed responsiveness by ipsilateral musimol was not affected by bicuculline applied to contralateral cortex. These results suggest that afferent transmission to VPM thalamus may be subjected to the interhemispheric modulation via ipsilateral cortex during inactivation of GABAergic neurons in contralateral SI cortex.
Animals ; Bicuculline ; GABA Agonists ; GABA Antagonists ; GABAergic Neurons ; gamma-Aminobutyric Acid ; Neurons ; Rats ; Somatosensory Cortex* ; Thalamus*

The echolocating big brown bats (Eptesicus fuscus) emit trains of frequency-modulated (FM) biosonar signals with duration, amplitude, repetition rate, and sweep structure changing systematically during interception of their prey. In the present study, the sound stimuli of temporally patterned pulse trains at three different pulse repetition rates (PRRs) were used to mimic the sounds received during search, approach, and terminal stages of echolocation. Electrophysiological method was adopted in recordings from the inferior colliculus (IC) of midbrain. By means of iontophoretic application of bicuculline, the effect of GABAergic inhibition on the intensity sensitivity of IC neurons responding to three different PRRs of 10, 30 and 90 pulses per second (pps) was examined. The rate-intensity functions (RIFs) were acquired. The dynamic range (DR) of RIFs was considered as a criterion of intensity sensitivity. Comparing the average DR of RIFs at different PRRs, we found that the intensity sensitivity of some neurons improved, but that of other neurons decayed when repetition rate of stimulus trains increased from 10 to 30 and 90 pps. During application of bicuculline, the number of impulses responding to the different pulse trains increased under all stimulating conditions, while the DR differences of RIFs at different PRRs were abolished. The results indicate that GABAergic inhibition was involved in modulating the intensity sensitivity of IC neurons responding to pulse trains at different PRRs. Before and during bicuculline application, the percentage of changes in responses was maximal in lower stimulus intensity near to the minimum threshold (MT), and decreased gradually with the increment of stimulus intensity. This observation suggests that GABAergic inhibition contributes more effectively to the intensity sensitivity of the IC neurons responding to pulse trains at lower sound level.
Acoustic Stimulation ; Animals ; Bicuculline ; pharmacology ; Chiroptera ; Echolocation ; Electrophysiological Phenomena ; GABA-A Receptor Antagonists ; pharmacology ; Inferior Colliculi ; cytology ; Neurons ; cytology