SCH50911 / Merck (MSD) - LARVOL DELTA

Brain carbon monoxide can suppress the rat micturition reflex through brain γ-aminobutyric acid receptors. (PubMed, Int J Urol) - "Brain CO can suppress the rat micturition reflex through brain γ-aminobutyric acid (GABA) receptors."

Journal • Preclinical • Reflex • Anesthesia • Solid Tumor

The role of GPR39 zinc receptor in the modulation of glutamatergic and GABAergic transmission. (PubMed, Pharmacol Rep) - "Our findings indicate the important role of glutamate/GABA signaling in the antidepressant-like effect of TC-G 1008 and imply that GPR39 regulates the balance between excitatory and inhibitory activity in the brain. Thus, we suggest the zinc-sensing receptor be considered an interesting new target for the development of novel antidepressants."

Journal • CNS Disorders • Depression • Psychiatry • CHI3L1 • DLG4

LACTOCOCCUS LACTIS NCDO2118 INCREASES GUT LUMINAL LEVELS OF GABA AND EXERTS VISCERAL ANTINOCICEPTIVE PROPERTIES VIA ITS ACTIVE GAD ENZYMATIC ACTIVITY: AN EFFECT MEDIATED BY GABAB RECEPTOR ACTIVATION AND SPECIFIC MICROBIOTA GENERA DISTURBANCES. (DDW 2022) - "A similar protocol was performed in rats treated by NCDO2118 plus SCH-50911 (a GABAB receptor antagonist, 3 mg/kg IP)...We pointed out the key role of the GAD activity for this antinociceptive effect. Specific genera enrichment observed in the gut microbiota could positively participate in GABA translocation through the gut barrier to reduce visceral hypersensitivity."

CNS Disorders • Immunology • Mood Disorders • Pain • Psychiatry

Treatment of γ-Hydroxybutyrate (GHB) Overdose with the GABA Antagonist SGS742. (PubMed, J Pharmacol Exp Ther) - "Additional studies with a second GABA antagonist SCH50911 demonstrated similar effects, producing reversal of respiratory depression but producing tremors and abnormal movements...Since the toxicodynamic effects of GHB, including respiratory depression and lethality, are mediated through GABA receptor agonism, GABA receptor antagonists may represent a therapeutic strategy to treat overdoses. This study demonstrates that while GABA receptor antagonists are effective as a pretreatment, they are less effective when administered at times after GHB administration and their administration is also associated with time- and dose-associated toxicity."

Journal • Anesthesia • CNS Disorders • Depression • Epilepsy • Movement Disorders • Psychiatry

Blockade of the GABAB receptor suppressed alcohol self-administration in rats: an effect similar to that produced by GABAB receptor activation. (PubMed, Behav Pharmacol) - "Accordingly, the present study was designed to investigate whether treatment with the GABAB receptor antagonist, SCH 50911, reproduced the suppressing effect of the GABAB receptor agonist, baclofen, and several positive allosteric modulators of the GABAB receptor on operant oral alcohol self-administration in rats. Similar data were collected in the 'sucrose' experiment. These results extend to alcohol self-administration with the notion that activation and blockade of GABAB receptor may produce unidirectional effects on reward-related behaviours; these similarities are discussed in terms of differential contribution of pre- and postsynaptic GABAB receptors."

Journal • Preclinical • Addiction (Opioid and Alcohol)

[VIRTUAL] Brain hydrogen sulfide suppresses the rat micturition reflex via brain GABA receptors (AUA 2021) - "In this study, we examined effects of centrally administered GYY4137 (GYY, H2S donor) and AOAA (H2S synthesis inhibitor) on the rat micturition reflex...In some rats, effects of ICV pretreated SR95531 (SR, GABAA antagonist, 0.1 nmol/rat) or SCH50911 (SCH, GABAB antagonist, 0.1 nmol/rat) on the GYY (10 nmol/rat, ICV)-induced responses were investigated... Brain H2S endogenously suppresses the rat micturition reflex via brain GABAA and GABAB receptors in rats. Thus, the brain H2S might be new therapeutic targets for neurogenic bladder overactivity."

Preclinical • Anesthesia

[VIRTUAL] Brain α7 nicotinic acetylcholine receptors are involved in suppression of the rat micturition reflex via brain GABA receptors (AUA 2021) - "In some rats, effects of icv pretreated mecamylamine (MEC, non-selective nAChR antagonist, 100 or 300 nmol/rat), methyllycaconitine (MLA, selective a7 nAChR antagonist, 30 or 100 nmol/rat), dihydro-ß-erythroidine (DHßE, selective a4ß2 nAChR antagonist, 100 or 300 nmol/rat), SR95531 (SR, GABAA antagonist, 0.03 and 0.1 nmol/rat) or SCH50911 (SCH, GABAB antagonist, 0.03 and 0.1 nmol/rat) on the EP (1 nmol/rat, icv)-induced responses were examined... Brain a7 nAChRs are involved in suppression of the rat micturition reflex via brain GABAA and GABAB receptors, therefore, brain a7 nAChRs might be new therapeutic targets for neurogenic bladder overactivity."

Preclinical • Anesthesia

Toxicokinetic/Toxicodynamic Interaction Studies in Rats between the Drugs of Abuse γ-Hydroxybutyric Acid and Ketamine and Treatment Strategies for Overdose. (PubMed, Pharmaceutics) - "SCH50911 (GABA receptor antagonist), but not naloxone, improved GHB-induced respiratory depression in the presence of ketamine. In conclusion, ketamine ingestion with GHB can result in significant TK/TD interactions. MCT inhibition and GABA receptor antagonism can serve as potential treatment strategies for GHB overdose when it is co-ingested with ketamine."

Journal • Preclinical • Anesthesia • CNS Disorders • Depression • Psychiatry

Stimulation of brain α7-nicotinic acetylcholine receptors suppresses the rat micturition through brain GABAergic receptors. (PubMed, Biochem Biophys Res Commun) - "The latter was suppressed by intracerebroventricularly pretreated methyllycaconitine (selective α7-nAChR antagonist), SR95531 (GABA antagonist), and SCH50911 (GABA antagonist), but not by dihydro-β-erythroidine (selective α4β2-nAChR antagonist). Intracerebroventricularly administered PHA568487 (selective α7-nAChR agonist) prolonged ICI without affecting MVP, similar to (±)-epibatidine. These results suggest that stimulation of brain α7-nAChRs suppresses the rat micturition through brain GABA/GABA receptors, independently of the sympatho-adrenomedullary outflow modulation."

Journal • Anesthesia

Exploring the binding mechanism of GABA receptor agonists and antagonists through in silico simulations. (PubMed, J Chem Inf Model) - "In this work, we have used the recent X-ray cocrystallization data of agonists (GABA and Baclofen) and antagonists (2-Hydroxysaclofen, SCH50911 and CGP54626) bound to GABA orthosteric site together with quantum biochemistry and the molecular fractionation with conjugate caps (MFCC) scheme to describe the individual contribution of each amino-acid residue involved in the GABA-ligand interaction, pointing out differences and similarities among the compounds...Finally, we predict the energetic relevance of the regions of the five ligands, as well as the influence of each protein lobe on GABA-ligand binding. These results bring important new information on the binding mechanism of the GABA receptor and should facilitate the development of new chemicals targeting this receptor."

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