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Chemical Compound Review

muscimol     5-(aminomethyl)-1,2-oxazol-3- one

Synonyms: Agarine, Pantherin, Agarin, Pantherine, Lopac-G-019, ...
 
 
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Disease relevance of Agarin

  • Improvement in tardive dyskinesia after muscimol therapy [1].
  • Both the (-)AP7- and muscimol-induced catalepsy were antagonized by coadministration of NMDA and the GABA antagonist bicuculline [2].
  • Bilateral, but not unilateral, injection of muscimol (200 pmol) into STN protected against limbic motor seizures evoked either by intravenous bicuculline or by focal application of bicuculline into anterior piriform cortex (area tempestas) [3].
  • After the chronic portacaval shunt and to a lesser extent in normal rats intraventricular muscimol resulted in chewing and eating behavior, ataxia and loss of balance that lasted 2 to 3 hr [4].
  • In rats developing hepatic encephalopathy, intraventricular muscimol shortened the time to precoma and coma by approximately 40% [4].
 

Psychiatry related information on Agarin

 

High impact information on Agarin

 

Chemical compound and disease context of Agarin

 

Biological context of Agarin

  • Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced 36Cl- uptake and generated cAMP with similar potencies (IC50 = 14.3 microM; EC50 = 6.2 microM, respectively) [20].
  • The stoichiometry of phosphorylation (mol of phosphate/mol of muscimol binding) catalyzed by cAMP-dependent protein kinase was 0.52 and that catalyzed by protein kinase C was 0.38 [21].
  • Injection of the potent GABA agonist muscimol (0.01-1 microgram) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 +/- 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of -52.7 +/- 5 mm Hg lasting for about 90 minutes [22].
  • These findings demonstrate that muscimol-induced inhibition of neuronal activity in the region of the DMH blocks air stress-induced increases in heart rate and arterial pressure, whereas similar treatment in the area of the PVN has no effect [23].
  • Using conventionally prepared washed membrane fractions from rat cerebral cortex, we have confirmed that in the presence of 200 mM NaBr [35S] TBPS binds to a high affinity population of binding sites (Kd 26 +/- 5 nM) and that muscimol inhibits [35S] TBPS binding (IC50 0.32 microM) allosterically [24].
 

Anatomical context of Agarin

  • In the rat, an intraseptal injection of the gamma-aminobutyric acid (GABA) agonist muscimol decreases the turnover rate of acetylcholine in the hippocampus and, during extinction of a food-reinforced lever-press response, increases extinction responding in a dose-dependent manner [25].
  • Recording from single cortical cells after they had recovered from the muscimol-induced blockade, we found a consistent shift in the responsiveness of the visual cortex in favor of the less-active, closed eye, while the normal shift in favor of the more-active, open eye was evident in regions not affected by the treatment [26].
  • When expressed in Xenopus laevis oocytes, the subunit functions efficiently, presumably as a homooligomeric complex and is activated by GABA or muscimol [27].
  • Mechanisms by which diazepam, muscimol, and other drugs change the content of cGMP in cerebellar cortex [28].
  • Within the arcuate nucleus, muscimol treatment increased the phosphorylation of CREB in both females and males [14].
 

Associations of Agarin with other chemical compounds

 

Gene context of Agarin

  • Immunocytochemical labeling of the receptors showed that the disappearance of receptor clusters in the somatic membrane as induced by muscimol stimulation was enhanced by Rac1 inactivation [34].
  • Similar results were obtained with the perfused rat pancreas; muscimol slightly inhibited glucagon release under various conditions, and bicuculline did not reverse the strong inhibition produced by 16.7 mM glucose [35].
  • When GnRH secretion is evoked by muscimol and NMDA, a time-related reduction of GnRH secretion is caused by antisense oligodeoxynucleotides for the beta subunit of the GABAA receptor and the NR2A subunit of the NMDA receptor, respectively [36].
  • 3. Reversible inactivation of the entorhinal cortex through muscimol infusion produced deficits in STM and a selective and rapid decrease in hippocampal ERK2 activation [37].
  • Other substances tested (10(-6) M) including thyrotropin-releasing hormone (TRH) and muscimol were without effect [38].
 

Analytical, diagnostic and therapeutic context of Agarin

  • Whereas the intraperitoneal injection of muscimol caused a reversible, dose-dependent decrease in net water absorption, bicuculline produced a reversible, dose-dependent increase in net water and ion absorption [13].
  • Vagotomy prevented the effect of intracerebroventricular muscimol [13].
  • Unilateral microinjection of a GABA(A) receptor agonist (muscimol, 200 pmol) into STN produced a site-dependent contralaterally directed postural asymmetry without locomotor activation [3].
  • Intranigral injection of 1.3 microliters 1 mM muscimol (150 ng) effected a local metabolic activation in the substantia nigra reticulata (by 111% compared to the control group) and in compacta (by 18%), as well as a distal activation in the contralateral reticulata (by 39%) and contralateral compacta (by 29%) [39].
  • Receptor currents were measured with the whole-cell patch-clamp technique during repetitive stimulation with 1 microm muscimol [34].

References

  1. Improvement in tardive dyskinesia after muscimol therapy. Tamminga, C.A., Crayton, J.W., Chase, T.N. Arch. Gen. Psychiatry (1979) [Pubmed]
  2. The rat ventromedial thalamic nucleus and motor control: role of N-methyl-D-aspartate-mediated excitation, GABAergic inhibition, and muscarinic transmission. Klockgether, T., Schwarz, M., Turski, L., Sontag, K.H. J. Neurosci. (1986) [Pubmed]
  3. Postural and anticonvulsant effects of inhibition of the rat subthalamic nucleus. Dybdal, D., Gale, K. J. Neurosci. (2000) [Pubmed]
  4. In vivo studies of GABAergic effects in experimental hepatic encephalopathy. Rzepczynski, D., Zieve, L., Lindblad, S., LaFontaine, D. Hepatology (1986) [Pubmed]
  5. Purinergic regulation of food intake. Levine, A.S., Morley, J.E. Science (1982) [Pubmed]
  6. Regulation of somatodendritic dopamine release in the ventral tegmental area by opioids and GABA: an in vivo microdialysis study. Klitenick, M.A., DeWitte, P., Kalivas, P.W. J. Neurosci. (1992) [Pubmed]
  7. Huntington's disease: treatment with muscimol, a GABA-mimetic drug. Shoulson, I., Goldblatt, D., Charlton, M., Joynt, R.J. Ann. Neurol. (1978) [Pubmed]
  8. The amygdala modulates memory consolidation of fear-motivated inhibitory avoidance learning but not classical fear conditioning. Wilensky, A.E., Schafe, G.E., LeDoux, J.E. J. Neurosci. (2000) [Pubmed]
  9. GABAergic modulation of descending inhibitory systems from the rostral ventromedial medulla (RVM). Dose-response analysis of nociception and neurological deficits. Gilbert, A.K., Franklin, K.B. Pain (2001) [Pubmed]
  10. GABA-mediated control of rat neostriatal tyrosine hydroxylase revealed by intranigral muscimol. Gale, K.N., Guidotti, A. Nature (1976) [Pubmed]
  11. Anticipatory activity in primary motor cortex codes memorized movement sequences. Lu, X., Ashe, J. Neuron (2005) [Pubmed]
  12. GABAergic stimulation regulates the phenotype of hippocampal interneurons through the regulation of brain-derived neurotrophic factor. Marty, S., Berninger, B., Carroll, P., Thoenen, H. Neuron (1996) [Pubmed]
  13. Central action of gamma-aminobutyric acid ligands to alter basal water and electrolyte absorption in the rat ileum. Fogel, R., Kaplan, R.B., Arbit, E. Gastroenterology (1985) [Pubmed]
  14. Excitatory versus inhibitory GABA as a divergence point in steroid-mediated sexual differentiation of the brain. Auger, A.P., Perrot-Sinal, T.S., McCarthy, M.M. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  15. delta-Aminolevulinic acid: influences on synaptic GABA receptor binding may explain CNS symptoms of porphyria. Müller, W.E., Snyder, S.H. Ann. Neurol. (1977) [Pubmed]
  16. Inhibition by gamma-amino-n-butyric acid and baclofen of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Tatsuta, M., Iishi, H., Baba, M., Nakaizumi, A., Ichii, M., Taniguchi, H. Cancer Res. (1990) [Pubmed]
  17. Comparison of interactions of [3H]muscimol, t-butylbicyclophosphoro[35S]thionate, and [3H]flunitrazepam with cloned gamma-aminobutyric acidA receptors of the alpha 1 beta 2 and alpha 1 beta 2 gamma 2 subtypes. Pregenzer, J.F., Im, W.B., Carter, D.B., Thomsen, D.R. Mol. Pharmacol. (1993) [Pubmed]
  18. Stimulation of prolactin and growth hormone secretion by muscimol, a gamma-aminobutyric acid agonist. Tamminga, C.A., Neophytides, A., Chase, T.N., Frohman, L.A. J. Clin. Endocrinol. Metab. (1978) [Pubmed]
  19. Effects of GABAergic agonists and antagonists on various ethanol-induced behavioral changes. Liljequist, S., Engel, J. Psychopharmacology (Berl.) (1982) [Pubmed]
  20. cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes. Heuschneider, G., Schwartz, R.D. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  21. Protein kinase C and cAMP-dependent protein kinase phosphorylate the beta subunit of the purified gamma-aminobutyric acid A receptor. Browning, M.D., Bureau, M., Dudek, E.M., Olsen, R.W. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  22. Antihypertensive effect of the GABA receptor agonist muscimol in spontaneously hypertensive rats. Role of the sympathoadrenal axis. Unger, T., Becker, H., Dietz, R., Ganten, D., Lang, R.E., Rettig, R., Schömig, A., Schwab, N.A. Circ. Res. (1984) [Pubmed]
  23. Muscimol acts in dorsomedial but not paraventricular hypothalamic nucleus to suppress cardiovascular effects of stress. Stotz-Potter, E.H., Willis, L.R., DiMicco, J.A. J. Neurosci. (1996) [Pubmed]
  24. [35S]-t-butylbicyclophosphorothionate binding sites are constituents of the gamma-aminobutyric acid benzodiazepine receptor complex. Supavilai, P., Karobath, M. J. Neurosci. (1984) [Pubmed]
  25. Behavioral and neurochemical differentiation of specific projections in the septal-hippocampal cholinergic pathway of the rat. Blaker, W.D., Peruzzi, G., Costa, E. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  26. Neural plasticity without postsynaptic action potentials: less-active inputs become dominant when kitten visual cortical cells are pharmacologically inhibited. Reiter, H.O., Stryker, M.P. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  27. Cloning and functional expression of a Drosophila gamma-aminobutyric acid receptor. Chen, R., Belelli, D., Lambert, J.J., Peters, J.A., Reyes, A., Lan, N.C. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  28. Mechanisms by which diazepam, muscimol, and other drugs change the content of cGMP in cerebellar cortex. Biggio, G., Brodie, B.B., Costa, E., Guidotti, A. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  29. Effects of gamma-aminobutyric acid on skate retinal horizontal cells: evidence for an electrogenic uptake mechanism. Malchow, R.P., Ripps, H. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  30. Gamma-aminobutyric acidA receptor function is inhibited by microtubule depolymerization. Whatley, V.J., Mihic, S.J., Allan, A.M., McQuilkin, S.J., Harris, R.A. J. Biol. Chem. (1994) [Pubmed]
  31. Lidocaine and muscimol microinjections in subthalamic nucleus reverse Parkinsonian symptoms. Levy, R., Lang, A.E., Dostrovsky, J.O., Pahapill, P., Romas, J., Saint-Cyr, J., Hutchison, W.D., Lozano, A.M. Brain (2001) [Pubmed]
  32. Effect of muscimol on glucose-stimulated somatostatin and insulin release from the isolated, perfused rat pancreas. Robbins, M.S., Grouse, L.H., Sorenson, R.L., Elde, R.P. Diabetes (1981) [Pubmed]
  33. ATP-Sensitive K+ Channels Regulate the Release of GABA in the Ventromedial Hypothalamus During Hypoglycemia. Chan, O., Lawson, M., Zhu, W., Beverly, J.L., Sherwin, R.S. Diabetes (2007) [Pubmed]
  34. Regulation of somatodendritic GABAA receptor channels in rat hippocampal neurons: evidence for a role of the small GTPase Rac1. Meyer, D.K., Olenik, C., Hofmann, F., Barth, H., Leemhuis, J., Brünig, I., Aktories, K., Nörenberg, W. J. Neurosci. (2000) [Pubmed]
  35. The influence of gamma-aminobutyric acid on hormone release by the mouse and rat endocrine pancreas. Gilon, P., Bertrand, G., Loubatières-Mariani, M.M., Remacle, C., Henquin, J.C. Endocrinology (1991) [Pubmed]
  36. Duality of glutamatergic and GABAergic control of pulsatile GnRH secretion by rat hypothalamic explants: I. Effects of antisense oligodeoxynucleotides using explants including or excluding the preoptic area. Bourguignon, J.P., Gérard, A., Purnelle, G., Czajkowski, V., Yamanaka, C., Lemaître, M., Rigo, J.M., Moonen, G., Franchimont, P. J. Neuroendocrinol. (1997) [Pubmed]
  37. Early Activation of Extracellular Signal-Regulated Kinase Signaling Pathway in the Hippocampus is Required for Short-Term Memory Formation of a Fear-Motivated Learning. Igaz, L.M., Winograd, M., Cammarota, M., Izquierdo, L.A., Alonso, M., Izquierdo, I., Medina, J.H. Cell. Mol. Neurobiol. (2006) [Pubmed]
  38. Effect of dopamine on amylase secretion from guinea pig pancreatic acinar cells in vitro. Xue, B.G., Hernandez, D.E. Life Sci. (1989) [Pubmed]
  39. Bilateral alterations in local cerebral glucose utilization following intranigral application of the GABAergic agonist muscimol. Dermon, C.R., Pizarro, P., Georgopoulos, P., Savaki, H.E. J. Neurosci. (1990) [Pubmed]
 
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