Protein Information

Name chloride channel (protein family or complex)
Synonyms chloride channel

Compound Information

Name strychnine
CAS strychnidin-10-one

Reference List

PubMed Abstract RScore(About this table)
16381810 Song W, Chattipakorn SC, McMahon LL: Glycine-gated chloride channels depress synaptic transmission in rat hippocampus. J Neurophysiol. 2006 Apr;95(4):2366-79. Epub 2005 Dec 28.

An inhibitory role for strychnine-sensitive glycine-gated chloride channels (GlyRs) in mature hippocampus is beginning to be appreciated.
Blockade of postsynaptic GlyRs with the chloride channel blocker 4, 4'-diisothiocyanatostilbene-2-2'-disulfonic acid (DIDS) or altering the chloride ion driving force in recorded cells attenuates the synaptic depression, strongly indicating that a postsynaptic mechanism is responsible.
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8600299 Galvez-Ruano E, Aprison MH, Robertson DH, Lipkowitz KB: Identifying agonistic and antagonistic mechanisms operative at the GABA receptor. J Neurosci Res. 1995 Dec;42(5):666-73.

Our data support a hypothesis for GABAergic antagonist activity which suggests that the antagonist simply binds to the recognition site and blocks the neurotransmitter, GABA, from entering this site thereby preventing the opening of the chloride channel; it just stays closed.
Moreover, we find a remarkedly different antagonistic mechanism exists for this phylogenetically newer inhibitory system in the central nervous system (CNS) than recently reported for strychnine and eight weaker glycine antagonists.
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15266648 Yoshida M, Fukuda S, Tozuka Y, Miyamoto Y, Hisatsune T: Developmental shift in bidirectional functions of taurine-sensitive chloride channels during cortical circuit formation in postnatal mouse brain. J Neurobiol. 2004 Aug;60(2):166-75.


In this study, by means of whole-cell patch-clamp recordings, we examined the effects of taurine on chloride channel receptors in neocortical neurons from early to late postnatal stages, which cover a critical period in cortical circuit formation.
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9927632 Moorhouse AJ, Jacques P, Barry PH, Schofield PR: The startle disease mutation Q266H, in the second transmembrane domain of the human glycine receptor, impairs channel gating. Mol Pharmacol. 1999 Feb;55(2):386-95.

Hyperekplexia (startle disease) results from mutations in the glycine receptor chloride channel that disrupt inhibitory synaptic transmission.
This was not accompanied by similar changes in agonist displacement of strychnine binding, suggesting that the mutation affects functions subsequent to ligand binding.
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9401974 Boehm S, Harvey RJ, von Holst A, Rohrer H, Betz H: Glycine receptors in cultured chick sympathetic neurons are excitatory and trigger neurotransmitter release. J Physiol. 1997 Nov 1;504 ( Pt 3):683-94.

The classical glycine receptor antagonist strychnine reversibly reduced glycine-induced currents, with half-maximal inhibition occurring at 62 nM.
The chloride channel blocker picrotoxin reduced glycine-evoked currents, with half-maximal effects at 348 microM.
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7538566 Grant GB, Dowling JE: A glutamate-activated chloride current in cone-driven ON bipolar cells of the white perch retina. J Neurosci. 1995 May;15(5 Pt 2):3852-62.

Thus, IGlu appears to involve a chloride channel activated by a glutamate receptor with transporter-like pharmacology.
IGlu was not blocked by 100 microM picrotoxin or 1 microM strychnine, indicating that it was not caused by inhibitory input.
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7874121 Buckwalter MS, Cook SA, Davisson MT, White WF, Camper SA: A frameshift mutation in the mouse alpha 1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death. Hum Mol Genet. 1994 Nov;3(11):2025-30.

Glra1 assembles into a pentameric complex with the beta subunit of the glycine receptor (3 alpha (1) 2 beta 5) to form a glycine-gated chloride channel.
This receptor is the major adult glycine receptor, and the site of action of the poison strychnine.
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11900860 Kondratskaya EL, Lishko PV, Chatterjee SS, Krishtal OA: BN52021, a platelet activating factor antagonist, is a selective blocker of glycine-gated chloride channel. Neurochem Int. 2002 Jun;40(7):647-53.

When co-applied with strychnine (STR), a competitive glycine receptor antagonist, BN52021 does not alter the IC50 value for strychnine.
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11278873 Shan Q, Haddrill JL, Lynch JW: Ivermectin, an unconventional agonist of the glycine receptor chloride channel. J Biol Chem. 2001 Apr 20;276(16):12556-64. Epub 2001 Jan 18.

Relative to glycine-gated currents, ivermectin-gated currents exhibited a dramatically reduced sensitivity to inhibition by strychnine, picrotoxin, and zinc.
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10670525 Sato Y, Son JH, Meizel S: The mouse sperm glycine receptor/chloride channel: cellular localization and involvement in the acrosome reaction initiated by glycine. J Androl. 2000 Jan-Feb;21(1):99-106.

The glycine-initiated AR was significantly inhibited by 50 nM strychnine, a neuronal GlyR antagonist.
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7689044 Siebler M, Pekel M, Koller H, Muller HW: Strychnine-sensitive glycine receptors in cultured primary neurons from rat neocortex. Brain Res Dev Brain Res. 1993 Jun 8;73(2):289-92.

The results provide evidence for a very early expression of glycine receptors on cortical neurons leading to a powerful chloride channel-operating capacity during early development.
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7925268 Langosch D, Laube B, Rundstrom N, Schmieden V, Bormann J, Betz H: Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia. EMBO J. 1994 Sep 15;13(18):4223-8.

Voltage-clamp recordings from the heterologously expressed mutants (alpha 1R271L or alpha 1R271Q) revealed 146- to 183-fold decreased potencies of glycine to activate the chloride channel, and significantly reduced maximal whole-cell currents as compared with wild-type receptors.
In contrast, the ability of the competitive antagonist strychnine to block glycine-induced currents was similar in all cases.
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9798943 Lynch JW, Jacques P, Pierce KD, Schofield PR: Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways. J Neurochem. 1998 Nov;71(5):2159-68.

Molecular mechanisms of zinc potentiation were investigated in recombinant human alpha1 glycine receptors (GlyRs) by whole-cell patch-clamp recording and [3H] strychnine binding assays.
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10698962 Wheeler M, Stachlewitz RF, Yamashina S, Ikejima K, Morrow AL, Thurman RG: Glycine-gated chloride channels in neutrophils attenuate calcium influx and superoxide production. FASEB J. 2000 Mar;14(3):476-84.

Moreover, strychnine (1 microM), an antagonist of the glycine-gated chloride channel in the central nervous system, reversed the effects of glycine (1 mM) on FMLP- or LPS-stimulated increases in [Ca (2+)](i).
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11238050 Dong Z, Venkatachalam MA, Weinberg JM, Saikumar P, Patel Y: Protection of ATP-depleted cells by impermeant strychnine derivatives: implications for glycine cytoprotection. Am J Pathol. 2001 Mar;158(3):1021-8.

Glycine and structurally related amino acids with activities at chloride channel receptors in the central nervous system also have robust protective effects against cell injury by ATP depletion.
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11380521 Patten D, Foxon GR, Martin KF, Halliwell RF: An electrophysiological study of the effects of propofol on native neuronal ligand-gated ion channels. Clin Exp Pharmacol Physiol. 2001 May-Jun;28(5-6):451-8.

Pharmacological evidence suggests that some of the clinical actions of propofol may be mediated, at least in part, by positive modulation of the GABA (A) receptor chloride channel.
To gain some insight into the effects of propofol at a range of native neuronal receptors, the present study has used an extracellular recording technique and determined its effects at GABA (A), 5-HT3, P2X and nicotinic acetylcholine (nACh) receptors of the rat isolated vagus nerve and the GABA (A) and strychnine-sensitive glycine receptor of the rat isolated optic nerve.
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9144769 Gready JE, Ranganathan S, Schofield PR, Matsuo Y, Nishikawa K: Predicted structure of the extracellular region of ligand-gated ion-channel receptors shows SH2-like and SH3-like domains forming the ligand-binding site. Protein Sci. 1997 May;6(5):983-98.

LGICs are pentamers with extracellular ligand-binding domains and form integral membrane ion channels that are selective for cations (acetylcholine and serotonin 5HT3 receptors) or anions (GABAA and glycine receptors and the invertebrate glutamate-binding chloride channel).
Using the glycine receptor alpha 1 subunit, which forms homopentamers, the monomeric and pentameric models define the agonist and antagonist (strychnine) binding sites to a deep crevice formed by an extended loop, which includes the invariant disulfide bridge, between the SH2 and SH3 domains.
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11962256 Yamashina S, Konno A, Wheeler MD, Rusyn I, Rusyn EV, Cox AD, Thurman RG: Endothelial cells contain a glycine-gated chloride channel. . Nutr Cancer. 2001;40(2):197-204.

Furthermore, the inhibitory effects of glycine were prevented by 1 microM strychnine, a glycine receptor antagonist, or when cells were incubated in Cl (-)-free buffer.
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14593111 Breitinger U, Breitinger HG, Bauer F, Fahmy K, Glockenhammer D, Becker CM: Conserved high affinity ligand binding and membrane association in the native and refolded extracellular domain of the human glycine receptor alpha1-subunit. J Biol Chem. 2004 Jan 16;279(3):1627-36. Epub 2003 Oct 30.

The strychnine-sensitive glycine receptor (GlyR) is a ligand-gated chloride channel composed of ligand binding alpha- and gephyrin anchoring beta-subunits.
81(1,1,1,1) Details
19861413 Vogel N, Kluck CJ, Melzer N, Schwarzinger S, Breitinger U, Seeber S, Becker CM: Mapping of disulfide bonds within the amino-terminal extracellular domain of the inhibitory glycine receptor. J Biol Chem. 2009 Dec 25;284(52):36128-36. Epub 2009 Oct 27.

The strychnine-sensitive glycine receptor (GlyR) is a ligand-gated chloride channel and a member of the superfamily of cysteine loop (Cys-loop) neurotransmitter receptors, which also comprises the nicotinic acetylcholine receptor (nAChR).
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12388211 Qu W, Ikejima K, Zhong Z, Waalkes MP, Thurman RG: Glycine blocks the increase in intracellular free Ca2+ due to vasoactive mediators in hepatic parenchymal cells. Am J Physiol Gastrointest Liver Physiol. 2002 Dec;283(6):G1249-56. Epub 2002 Aug 14.

Low-dose strychnine, an antagonist of glycine-gated chloride channel in the central nervous system, partially reversed the inhibition by glycine.
Low-dose strychnine, an antagonist of glycine-gated chloride channel in the central nervous system, partially reversed the inhibition by glycine.
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18835373 Giambelluca MS, Gende OA: Effect of glycine on the release of reactive oxygen species in human neutrophils. Int Immunopharmacol. 2009 Jan;9(1):32-7. Epub 2008 Oct 1.

The inhibitory effect was insensitive to strychnine and also obtained when PMA was used as stimulant.
This study demonstrated that glycine impaired the activation of oxidative burst independently of glycine-gated chloride channel, presumably at the membrane level.
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7830058 Widdowson PS, Trainor A, Lock EA: NMDA receptors in rat cerebellum and forebrain: subtle differences in pharmacology and modulation. J Neurochem. 1995 Feb;64(2):651-61.


In the cerebellum, however, [3H] glycine bound to a second site with a 10-fold lower affinity and with a pharmacology that resembled that of the glycine/strychnine chloride channel. [3H]-Glutamate binding was not affected by glycine agonists or antagonists, nor was [3H] glycine binding affected by glutamate agonists in either forebrain or cerebellum.
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17173871 Molchanova SM, Oja SS, Saransaari P: Inhibitory effect of taurine on veratridine-evoked D-[3H] aspartate release from murine corticostriatal slices: involvement of chloride channels and mitochondria. Brain Res. 2007 Jan 26;1130(1):95-102. Epub 2006 Dec 14.


The glycine receptor antagonist strychnine and the GABA (A) receptor antagonist bicuculline did not block the taurine effect, although picrotoxin, a less specific blocker of agonist-gated chloride channels, completely prevented the effect of taurine on veratridine-induced D-[3H] aspartate release.
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8821829 Venkatachalam MA, Weinberg JM, Patel Y, Saikumar P, Dong Z: Cytoprotection of kidney epithelial cells by compounds that target amino acid gated chloride channels. Kidney Int. 1996 Feb;49(2):449-60.

Two classes of compounds showed cytoprotective activity in this system: (1) ligands at chloride channel receptors, such as glycine, strychnine and avermectin B1a; (2) chloride channel blockers, including cyanotriphenylboron and niflumic acid, both of which are known to bind to channel domains of CNS glycine receptors.
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11212343 Wheeler MD, Ikejema K, Enomoto N, Stacklewitz RF, Seabra V, Zhong Z, Yin M, Schemmer P, Rose ML, Rusyn I, Bradford B, Thurman RG: Glycine: a new anti-inflammatory immunonutrient. Cell Mol Life Sci. 1999 Nov 30;56(9-10):843-56.

Pharmacological analysis using a GlyR antagonist strychnine, chloride-free buffer, and radiolabeled chloride has provided convincing evidence to support the hypothesis that many white blood cells contain a glycine-gated chloride channel with properties similar to the spinal cord GlyR.
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15888962 Leewanich P, Tohda M, Takayama H, Sophasan S, Watanabe H, Matsumoto K: Corymine potentiates NMDA-induced currents in Xenopus oocytes expressing NR1a/NR2B glutamate receptors. J Pharmacol Sci. 2005 May;98(1):58-65. Epub 2005 May 12.


Previous studies demonstrated that corymine, an indole alkaloid isolated from the leaves of Hunter zeylanica, dose-dependently inhibited strychnine-sensitive glycine-induced currents.
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9747898 Peters SM, de Jong MD, Bindels RJ, van Os CH, Wetzels JF: Effects of renal cytoprotective agents on erythrocyte membrane stability. Life Sci. 1998;63(11):975-83.


Freshly isolated rabbit erythrocytes were subjected to a hypotonic shock, and the protective effects of various calcium channel blockers, phospholipase inhibitors, free fatty acids, the NO-synthase inhibitor L-NAME, the amino acid glycine and its receptor-analogue strychnine, and two chloride channel blockers were examined.
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16888071 Dombkowski RA, Doellman MM, Head SK, Olson KR: Hydrogen sulfide mediates hypoxia-induced relaxation of trout urinary bladder smooth muscle. J Exp Biol. 2006 Aug;209(Pt 16):3234-40.


Inhibitors of neuronal mechanisms, tetrodotoxin, strychnine and N-vanillylnonanamide were likewise ineffective.
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7500379 Galvez-Ruano E, Lipkowitz KB, Aprison MH: On identifying a second molecular antagonistic mechanism operative at the glycine receptor. J Neurosci Res. 1995 Aug 15;41(6):775-81.

In group 1 (strychnine, brucine, Pitrazepin, and bicuculline methobromide) the antagonist contains two or three sites that can electrostatically bind to the three comparable groups of opposite charge in the recognition site where the natural neurotransmitter binds, thus opening the chloride channel.
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9019549 Galante RJ, Kubin L, Fishman AP, Pack AI: Role of chloride-mediated inhibition in respiratory rhythmogenesis in an in vitro brainstem of tadpole, Rana catesbeiana. J Physiol. 1996 Apr 15;492 ( Pt 2):545-58.

To investigate the role of chloride channel-dependent inhibitory mechanisms mediated by GABA (A) and/or glycine receptors on fictive lung and gill ventilation, we superfused the isolated brainstems with agonists, antagonists (bicuculline and/or strychnine) or a chloride-free solution while recording multi-unit activity from the facial motor nucleus. 2.
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9636118 Cleland TA, Selverston AI: Inhibitory glutamate receptor channels in cultured lobster stomatogastric neurons. J Neurophysiol. 1998 Jun;79(6):3189-96.


The IGluR was weakly blocked by the chloride channel blocker furosemide and the excitatory glutamate receptor antagonist6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), but was not inhibited by bicuculline methiodide, strychnine, kynurenic acid, gamma--glutamylglycine, or aspartate.
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10960447 Zhang Y, Ikejima K, Honda H, Kitamura T, Takei Y, Sato N: Glycine prevents apoptosis of rat sinusoidal endothelial cells caused by deprivation of vascular endothelial growth factor. Hepatology. 2000 Sep;32(3):542-6.

Furthermore, strychnine (1 micromol/L), a glycine receptor antagonist, inhibited this effect of glycine, suggesting the possible involvement of the glycine receptor/chloride channel in the mechanism.
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12803134 Wang DS, Zhu HL, Li JS: Beta-alanine acts on glycine receptors in the rat sacral dorsal commissural neurons. Int J Neurosci. 2003 Mar;113(3):293-305.

Strychnine and the chloride channel blocker picrotoxin suppressed the I beta-ALA in a concentration-dependent manner with the IC50 values of 0.19 microM and 343.6 microM, respectively.
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9138273 Nagatomi A, Sakaida I, Matsumura Y, Okita K: Cytoprotection by glycine against hypoxia-induced injury in cultured hepatocytes. Liver. 1997 Apr;17(2):57-62.

Chloride-channel inhibitors [anthracene-9-carboxylic acid (A9C), furosemide, and strychnine] also significantly reduced hepatocellular death induced by hypoxia.
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10564180 Wheeler MD, Thurman RG: Production of superoxide and TNF-alpha from alveolar macrophages is blunted by glycine. Am J Physiol. 1999 Nov;277(5 Pt 1):L952-9.

Like the glycine-gated chloride channel in the central nervous system, the effects of glycine on [Ca (2+)](i) were both strychnine sensitive and chloride dependent.
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15081878 Jensen AA, Kristiansen U: Functional characterisation of the human alpha1 glycine receptor in a fluorescence-based membrane potential assay. Biochem Pharmacol. 2004 May 1;67(9):1789-99.

In the patch-clamp assay, the alpha1 GlyR exhibited the properties expected from a strychnine-sensitive glycine-gated chloride channel.
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11714703 Zheng Y, Hirschberg B, Yuan J, Wang AP, Hunt DC, Ludmerer SW, Schmatz DM, Cully DF: Identification of two novel Drosophila melanogaster histamine-gated chloride channel subunits expressed in the eye. J Biol Chem. 2002 Jan 18;277(3):2000-5. Epub 2001 Nov 19.

Histamine-activated currents were not blocked by picrotoxinin, fipronil, strychnine, or the H2 antagonist cimetidine.
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19617896 Wang HD, Lu XX, Lu DX, Qi RB, Wang YP, Fu YM, Wang LW: Glycine inhibits the LPS-induced increase in cytosolic Ca2+ concentration and TNFalpha production in cardiomyocytes by activating a glycine receptor. Acta Pharmacol Sin. 2009 Aug;30(8):1107-14. Epub 2009 Jul 20.

The present study investigated the effect of GLY on cytosolic calcium concentration ([Ca2+] c) and tumor necrosis factor-alpha (TNFalpha) production in cardiomyocytes exposed to LPS, as well as whether the glycine-gated chloride channel is involved in this process.
GLY did not inhibit TNFalpha production induced by LPS at concentrations below 10 ng/mL but did significantly decrease TNFalpha release stimulated by 100 microg/mL LPS and prevented an LPS-induced increase in [Ca2+] c, which was reversed by strychnine, a glycine receptor antagonist.
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10605009 Stachlewitz RF, Li X, Smith S, Bunzendahl H, Graves LM, Thurman RG: Glycine inhibits growth of T lymphocytes by an IL-2-independent mechanism. . J Immunol. 2000 Jan 1;164(1):176-82.

The effect of glycine was dependent on extracellular chloride and reversed by strychnine, an antagonist of the glycine-gated chloride channel.
The effect of glycine was dependent on extracellular chloride and reversed by strychnine, an antagonist of the glycine-gated chloride channel.
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18690053 Grudzinska J, Schumann T, Schemm R, Betz H, Laube B: Mutations within the agonist-binding site convert the homomeric alpha1 glycine receptor into a Zn2+-activated chloride channel. Channels. 2008 Jan-Feb;2(1):13-8. Epub 2008 Mar 12.

The divalent cation Zn2+ has been shown to regulate inhibitory neurotransmission in the mammalian CNS by affecting the activation of the strychnine-sensitive glycine receptor (GlyR).
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9227496 Ikejima K, Qu W, Stachlewitz RF, Thurman RG: Kupffer cells contain a glycine-gated chloride channel. . Am J Physiol. 1997 Jun;272(6 Pt 1):G1581-6.

Low concentrations of strychnine (1 microM), a glycine receptor antagonist, reversed the inhibitory effect of glycine completely; however, high concentrations of strychnine (1 mM) mimicked glycine.
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11500467 Li X, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG: Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Infect Immun. 2001 Sep;69(9):5883-91.

The inhibitory effect of glycine was reversed by low concentrations of strychnine or chloride-free buffer, and it increased radiolabeled chloride influx nearly fourfold, an effect also inhibited by strychnine.
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9823766 Seabra V, Stachlewitz RF, Thurman RG: Taurine blunts LPS-induced increases in intracellular calcium and TNF-alpha production by Kupffer cells. J Leukoc Biol. 1998 Nov;64(5):615-21.

Recently, it was shown that Kupffer cells contain a glycine-gated chloride channel.
This effect was reversed by strychnine (1 microM) and was prevented when chloride was removed from the extracellular media.
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17567469 Yamashina S, Ikejima K, Rusyn I, Sato N: Glycine as a potent anti-angiogenic nutrient for tumor growth. J Gastroenterol Hepatol. 2007 Jun;22 Suppl 1:S62-4.

Further, the inhibitory effects of glycine were prevented by low concentrations of strychnine (1 micromol/L) or incubation with chloride-free buffer.
Furthermore, mRNA 92% identical to the beta-subunit of the glycine-gated chloride channel from spinal cord was identified in endothelial cells using reverse transcription-polymerase chain reaction.
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8137816 Taleb O, Betz H: Expression of the human glycine receptor alpha 1 subunit in Xenopus oocytes: apparent affinities of agonists increase at high receptor density. EMBO J. 1994 Mar 15;13(6):1318-24.

The inhibitory glycine receptor (GlyR) is a ligand-gated chloride channel, which mediates post-synaptic inhibition in spinal cord and other brain regions.
The low-affinity receptors were readily blocked by nM concentrations of the competitive antagonist strychnine, whereas the high-affinity receptors were more resistant to antagonism by this alkaloid.
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12718443 Zhang K, Weinberg JM, Venkatachalam MA, Dong Z: Glycine protection of PC-12 cells against injury by ATP-depletion. Neurochem Res. 2003 Jun;28(6):893-901.

Of interest, strychnine, an antagonist of glycine receptor, was also protective.
The results, while suggesting the involvement of glycine receptor in cytoprotection, indicate that chloride channel activity of the receptor is dispensable.
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17308985 Trailovic SM, Varagic VM: The effect of ivermectin on convulsions in rats produced by lidocaine and strychnine. Vet Res Commun. 2007 Oct;31(7):863-72.

In nematodes, the target site of ivermectin's action is glutamate-gated chloride-channel receptor and GABA receptor.
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