GYKI 52466 (hydrochloride)
(Synonyms: AMPA受体选择性阻断剂前体) 目录号 : GC49255
An allosteric AMPA receptor antagonist
Cas No.:192065-56-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
GYKI 52466 is an allosteric AMPA receptor antagonist.1 It selectively inhibits AMPA-induced inward currents (IC50 = 7.5 µM) over NMDA- or GABA-induced inward currents in primary rat hippocampal neurons at 50 µM but also inhibits kainate-induced inward currents in the same cells (IC50 = 11 µM).2 GYKI 52466 (10 µM) reduces the amplitude of spontaneous excitatory postsynaptic currents (EPSCs) in the same cells. It increases the latency to seizure onset and reduces mortality in a rat model of generalized tonic-clonic seizures induced by 4-aminopyridine when administered at doses of 25 and 50 mg/kg.1 GYKI 52466 (30 mg/kg) prevents neuronal damage in the CA1 region of the hippocampus in a rat model of global ischemia-reperfusion injury induced by four-vessel occlusion.3
1.Weiczner, R., Krisztin-PÉva, B., and MihÁly, A.Blockade of AMPA-receptors attenuates 4-aminopyridine seizures, decreases the activation of inhibitory neurons but is ineffective against seizure-related astrocytic swellingEpilepsy Res.78(1)22-32(2008) 2.Donevan, S.D., and Rogawski, M.A.GYKI 52466, a 2,3-benzodiazepine, is a highly selective, noncompetitive antagonist of AMPA/kainate receptor responsesNeuron10(1)51-59(1993) 3.Block, F., Schmitt, W., and Schwarz, M.Pretreatment but not posttreatment with GYKI 52466 reduces functional deficits and neuronal damage after global ischemia in ratsJ. Neurol. Sci.139(2)167-172(1996)
| Cas No. | 192065-56-8 | SDF | |
| 别名 | AMPA受体选择性阻断剂前体 | ||
| Canonical SMILES | CC1=NN=C(C2=CC=C(N)C=C2)C3=C(C=C4OCOC4=C3)C1.Cl | ||
| 分子式 | C17H15N3O2·HCl | 分子量 | 329.8 |
| 溶解度 | Methanol: 1 mg/ml | 储存条件 | -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0321 mL | 15.1607 mL | 30.3214 mL |
| 5 mM | 0.6064 mL | 3.0321 mL | 6.0643 mL |
| 10 mM | 0.3032 mL | 1.5161 mL | 3.0321 mL |
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Effect of the non-NMDA receptor antagonist GYKI 52466 on the microdialysate and tissue concentrations of amino acids following transient forebrain ischaemia
J Neurochem 1994 Apr;62(4):1458-67.PMID:7907651DOI:10.1046/j.1471-4159.1994.62041458.x.
The effect of the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) on ischaemia-induced changes in the microdialysate and tissue concentrations of glutamate, aspartate, and gamma-aminobutyric acid (GABA) was studied in rats. Twenty minutes of four-vessel occlusion resulted in a transient increase in microdialysate levels of glutamate, aspartate, and GABA in striatum, cortex, and hippocampus. Administration of GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min intravenously starting 20 min before onset of ischaemia) inhibited ischaemia-induced increases in microdialysate glutamate and GABA in striatum without affecting the increases in hippocampus or cortex. Twenty minutes of four-vessel occlusion resulted in immediate small decreases and larger delayed (72 h) decreases in tissue levels of glutamate and aspartate. Transient increases in tissue levels of GABA were shown in all three structures at the end of the ischaemic period. At 72 h, after the ischaemic period, significantly reduced GABA levels were observed in striatum and hippocampus. GYKI 52466, given under identical conditions as above, augmented the ischaemia-induced decrease in striatal tissue levels of glutamate and aspartate, without significantly affecting the decreases in hippocampus and cortex. Twenty minutes of ischaemia resulted in a large increase in microdialysate dopamine in striatum. GYKI 52466 failed to inhibit this increase. Kainic acid (500 microM infused through the probe for 20 min) caused increases in microdialysate glutamate and aspartate in the striatum. GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min) completely inhibited the kainic acid-induced glutamate release. In conclusion, the action of the non-NMDA antagonist, GYKI 52466, in the striatum is different from that in the cortex and hippocampus. The inhibition by GYKI 52466 of ischaemia-induced and kainate-induced increases in microdialysate glutamate concentration in the striatum may be related to the neuroprotection provided by GYKI 52466 in this region.
GYKI 52466 and related 2,3-benzodiazepines as anticonvulsant agents in DBA/2 mice
Eur J Pharmacol 1995 Dec 29;294(2-3):411-22.PMID:8750701DOI:10.1016/0014-2999(95)00561-7.
The behavioural and anticonvulsant effects of several 1-aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones (2,3-BZs) and of 11b-aryl-7,11-dihydro-3-phenyl[1,2,4]oxadiazolo[5,4-a][2,3]benz odiazepin-6-ones (2,3-OBZs) were studied after intraperitoneal (i.p.) administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. The seizures were evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a hemispheric Perspex dome. The 2,3-benzodiazepines studied after 30 min pretreatment were generally less potent than the related derivative 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) except 3,5-dihydro-7,8-dimethoxy-1-phenyl-4H-2,3-benzodiazepin-4-one (2,3-BZ-2) and 2,3-BZ-2M (3-methyl derivative of 2,3-BZ-2) which showed comparable activity. Thirty minutes after i.p. administration of 2,3-benzodiazepines, the rank order of potency for anticonvulsant activity against clonus was 2,3-BZ-2 > GYKI 52466 > 2,3-BZ-2M > 2,3-BZ-1 > 2,3-BZ-3, > 2,3-OBZ-1, > 2,3-OBZ-2 2,3-OBZ-3. The intracerebroventricular (i.c.v.) injection of aniracetam on it own (12.5 - 100 nmol/mouse) had no convulsant activity, but it reversed the anticonvulsant effects of some 2,3-benzodiazepines. In particular, the pharmacological actions of GYKI 52466, 2,3-BZ-2 and 2,3-BZ-2M, which proved to be the most potent 2,3-benzodiazepine derivatives as anticonvulsants, were significantly reduced by an i.c.v. pretreatment with aniracetam (50 nmol/mouse). Concomitant treatment with aniracetam (50 nmol/mouse) shifted to the right the dose-response curves and significantly increased the ED50 values for GYKI 52466, 2,3-BZ-2 and 2,3-BZ-2M. After 30 min pretreatment 2,3-BZ-2 showed a similar potency to GYKI 52466 in antagonizing seizures induced by i.c.v. administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), thus suggesting a clear involvement of AMPA receptors in the anticonvulsant activity of these compounds. In addition, 2,3-BZ-2 and 2,3-BZ-2M showed anticonvulsant properties longer lasting than GYKI 52466.
GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] and the anticonvulsive activity of conventional antiepileptics against pentetrazol in mice
Mol Chem Neuropathol 1998 Apr;33(3):149-62.PMID:9642669DOI:10.1007/BF02815178.
Excitatory amino acids participate in the generation of seizure activity. Consequently, the effects of GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride], an antagonist of glutamate-mediated events, on the protective activity of conventional antiepileptic drugs against pentetrazol were studied. GYKI 52466 (up to 10 mg/kg, i.p.) did not affect the clonic phase of pentetrazol (injected s.c. at its CD97 of 90 mg/kg) convulsions. Only the antipentetrazol activity of valproate (100 mg/kg) was enhanced by GYKI 52466 (10 mg/kg)--the percentage of mice protected was significantly increased from 20 to 90%. The anticonvulsive activity of clonazepam (at 0.01), ethosuximide (at 50), and phenobarbital (at 2.5 mg/kg) was not modified by GYKI 52466 (up to 10 mg/kg). The combination of valproate (100 mg/kg) with GYKI 52466 (10 mg/kg) did not affect the performance of mice evaluated in the chimney test. However, this combination resulted in significant memory deficits, measured in the passive avoidance task. In no case did GYKI 52466 (10 mg/kg) affect either total or free plasma levels of antiepileptic drugs (as measured by immunofluorescence), so a pharmacokinetic interaction is not probable. Finally, the interaction of the non-NMDA receptor antagonist with antiepileptic drugs does not seem promising in the pentetrazol test, recognized as a model of human myoclonic epilepsy.
Protection against non-NMDA receptor-mediated excitotoxicity by GYKI 52466 in mature telencephalic cultures of the rat
Neurobiology (Bp) 1996;4(1-2):59-72.PMID:9116695doi
The neuroprotective effect of 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466), a recently developed non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate antagonist was demonstrated against quisqualate (10 or 15 microM) and AMPA (20 microM) excitotoxicity in mature (17-20 days in vitro) cultures of rat embryonic telencephalic cells. GYKI 52466 attenuated quisqualate (15 microM) or AMPA (20 microM) neurotoxicity in a dose-dependent manner with IC50 of 16 microM and 10 microM, respectively.
GYKI 52466 blocks the increase in extracellular glutamate induced by ischaemia
Neuroreport 1992 Mar;3(3):235-8.PMID:1355369DOI:10.1097/00001756-199203000-00004.
In vivo microdialysis has been used to study the effect of pre- or post-ischaemic administration of the non-NMDA antagonist 1-(4-amino-phenyl)-4-methyl-7, 8-methyl-endioxyl-5H-2,3- benzodiazepine hydrochloride (GYKI 52466), on the increases in extracellular glutamate levels induced by 20 minutes of four vessel occlusion in rats. In control rats, ischaemia resulted in transient increases in glutamate (4 fold), aspartate (6 fold) and gamma-aminobutyric acid (GABA) (15 fold) and decreases in glutamine (0.5 fold). Intravenous administration of GYKI 52466 (10 mg kg-1 bolus followed by 10 mg kg-1 h-1 infusion) beginning 20 minutes prior to the induction of ischaemia abolished ischaemia-induced glutamate release without affecting the increases in aspartate and GABA and the decrease in glutamine. Administration of GYKI 52466 immediately post-ischaemia resulted in a more rapid return of glutamate levels to basal values.