Disease relevance of Lopac-S-106

• The administration of GABAa antagonist gabazine enhances the occurrence of the epileptic seizures, slightly increases LMA but decreases myoclonia [1].
• The effects of GABAb antagonist 5-aminovalleric acid (5-AVA) or GABAa antagonist gabazine administrations in the globus pallidus (GP) on locomotor and motor hyperactivity (LMA) and myoclonia expressions in the model of the rat submitted to 8 MPa of helium-oxygen breathing mixture were analyzed [1].

High impact information on Lopac-S-106

• Using c-Fos as a marker of neuronal activation, we identified a possible role for the tuberomammillary nucleus (TMN): when gabazine was microinjected directly into the TMN, it attenuated the sedative response to GABAergic agents [2].
• Single-channel studies show that the gabazine-insensitive GABAA receptors have a lower unitary conductance (12 pS) than that estimated for synaptic receptors [3].
• Application of the muscarinic agonist pilocarpine mimicked the effect of IPSPs on MC maximal firing rate, and action potential height and slope, and this was reversed by the GABA(A) antagonist gabazine [4].
• Both types of events were blocked by gabazine, but only outward currents were significantly affected by the gap junction blocker carbenoxolone, indicating that outward events originated in electrically coupled neurons [5].
• Here, we examined whether synaptic inhibition entrains approximately 200 Hz network ripples by applying the GABA(A) receptor antagonist gabazine to CA1 minislices of mouse hippocampus [6].

Biological context of Lopac-S-106

• Strychnine acting with an IC50 approximately = 33 nM, eliminated residual fast inhibition during selective GABA(A) receptor blockade with gabazine [7].
• The remaining mPSCs had much slower kinetics (decay time = 19.6 ms) and were GABAergic [miniature inhibitory postsynaptic currents (mIPSCs)] as they were blocked by gabazine (3 microM) but not by strychnine (3-10 microM) [8].
• Both rat and human LC neurons have a high density of binding sites for the pyridazinyl-GABA derivative [3H]SR 95531 (gabazine, a GABAA receptor antagonist for low affinity GABA recognition sites) [9].
• Focal application of gabazine (25 muM) to cardiac vagal neurons in vitro did not change the frequency of firing in spontaneously active neurons or the resting membrane potential; however, picrotoxin (100 muM) significantly depolarized cardiac vagal neurons and increased their firing [10].
• However, when the excitatory postsynaptic potential was pharmacologically isolated by adding 10 microM gabazine (GABA(A) receptor antagonist) to the perfusate, 1 microM galantamine potentiated the subthreshold excitatory postsynaptic potentials into action potentials [11].

Anatomical context of Lopac-S-106

• Gabazine, a selective GABA(A) receptor antagonist, totally blocked evoked IPSCs in CA3 pyramidal cells [12].
• Injections of 3H-gabazine in the L4-L5 region at P3 confirmed that gabazine binding was restricted to the lumbar spinal cord [13].
• The effects of spinalization were consistent with gabazine facilitation of ventral root potentials observed in isolated neonatal spinal cord [13].
• To investigate whether functional GABA(A)R-mediated inhibition does indeed undergo postnatal regulation at the level of dorsal horn circuits, we applied the selective GABA(A)R antagonist gabazine to the spinal cord in anesthetized rat pups [postnatal day (P) 3 or 21] while recording spike activity in single lumbar dorsal horn cells in vivo [14].
• GABA-A receptor (bicuculline and Gabazine) and glycine receptor (strychnine) antagonists were applied directly to the cervical spinal cord (C3-C7), while bilateral phrenic nerve motor output was recorded [15].

Associations of Lopac-S-106 with other chemical compounds

• Excitatory postsynaptic currents (EPSCs) evoked by focal electrical stimulation were isolated by incubation with gabazine and strychnine, and inhibitory postsynaptic currents (IPSCs) were isolated with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) [16].
• Bicuculline, gabazine and kainic acid ejections specifically into the pontine sublaterodorsal nucleus (SLD) induced within a few minutes a PS-like state characterized by a continuous muscle atonia, low voltage EEG and a lack of reaction to stimuli [17].
• During N-methyl-D-aspartate (NMDA)-induced fictive locomotion (ventral root recordings in the isolated spinal cord), gabazine (0.1-100 microM) significantly increased the burst rate up to twofold, without changes in regularity or "burst quality." Gabazine had a proportionately greater effect at higher initial burst rates [18].
• In the presence of TTX (1 microM), and blockers of excitatory and inhibitory fast synaptic transmission [gabazine 5 microM, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) 10 microM, and (+/-)-2-amino-5-phosphonopentanoic acid (APV) 50 microM], the inward current induced by PE persisted (EC(50) = 9 microM), whereas that of Isop was absent [19].
• In addition, kynurenic acid abolished the sympathoexcitatory and pressor responses to microinjection of gabazine into the PVN in both SHRs and WKY rats [20].

Gene context of Lopac-S-106

• Furthermore, its inhibitory effect in the full disinhibition model of epileptiform activity (10 microM gabazine + 10 microM CGP55845) was occluded by the SK channel blocker apamin (300 nM-1 microM) which in its own right increased the duration and reduced the frequency of individual epileptiform bursts [21].

Analytical, diagnostic and therapeutic context of Lopac-S-106

• In the absence of TTX, excitatory PSCs evoked by focal electrical stimulation were isolated by application of gabazine and strychnine [8].
• Intrathecal gabazine also produced an increase in the cutaneous evoked electromyography (EMG) response of the biceps femoris in P21 rates but lowering the response in neonates [13].
• In contrast to gabazine, iontophoresis of the less potent GABA(A)-antagonist BIC often resulted in substantial broadening of frequency tuning for pure tones and an elimination of synchronized responses to AM tones, particularly with high ejecting currents [22].

References