Cyclothiazide acts as a positive allosteric modulator for AMPA receptors and is commonly employed to prevent the desensitization of AMPA receptors, whether they are native or expressed in a heterologous system. It is recognized for its rapid inhibition of desensitization in AMPA receptors and a more gradual enhancement of AMPA-mediated currents[1].
Cyclothiazide/环噻嗪 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HEK 293 cells
100 μM
30 s
To study the effect of CTZ on single-channel properties, results showed CTZ increased the mean open time and burst frequency
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2943-7.
HEK 293 cells
50 μM
To study the effect of CTZ on AMPA receptor affinity, results showed CTZ decreased the EC50 value of AMPA by ∼8-fold
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2943-7.
HEK 293 cells
100 μM
4 s
To study the potentiating effect of CTZ on AMPA currents, results showed CTZ increased the peak AMPA currents by 90-fold
Proc Natl Acad Sci U S A. 2006 Feb 21;103(8):2943-7.
High concentration of CTZ almost completely abolished IPSCs.
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13025-9.
Hippocampal microisland cultured neurons
30 μM
CTZ significantly inhibited the amplitude of IPSCs.
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13025-9.
Hippocampal microisland cultured neurons
100 μM
60 seconds
CTZ reversibly inhibited GABA A receptor-mediated inhibitory postsynaptic currents (IPSCs) and GABA-induced membrane currents in a dose-dependent manner. Single-channel analysis showed that CTZ significantly reduced the open probability of GABA A receptor channels.
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13025-9.
cultured superior colliculus neurones
3-300 μM
Cyclothiazide dramatically slowed desensitization of AMPA-induced currents and potentiated steady state currents (EC50 10.0±2.5 μM) to a much greater degree than peak currents. Both Ton and Toff were also increased by cyclothiazide in a concentration-dependent manner (EC50: Ton 42.1±4.5 μM; Toff 31.6±6.6 μM).
Br J Pharmacol. 1996 Mar;117(6):1209-21.
rat hippocampal synaptosomes
10μM
2 min
In the presence of cyclothiazide, AMPA elicited a dose-dependent increase in K+-stimulated [3H]-L-glutamate release but had no effect on basal release. This stimulation was blocked by CNQX and GYKI52466.
Br J Pharmacol. 1994 Oct;113(2):339-41.
bovine chromaffin cells
30-500 μM
2 s
To investigate the inhibitory effect of Cyclothiazide on neuronal-type nicotinic acetylcholine receptors (AChR) in bovine chromaffin cells. Results showed that Cyclothiazide dose-dependently inhibited the ACh-evoked peak current with little voltage-dependency.
Br J Pharmacol. 1995 Feb;114(3):648-55.
hippocampal neurons
5 μM
10 days
epileptiform activities were also observed after long-term low concentration CTZ treatment
J Physiol. 2006 Mar 15;571(Pt 3):605-18.
hippocampal neurons
20-50 μM
1-2 h
high concentration CTZ effectively elicited epileptiform activities after short-term treatment
J Physiol. 2006 Mar 15;571(Pt 3):605-18.
hippocampal neurons
5 μM
48 h
induced epileptiform activity in the majority of neurons (80%), which lasted more than 48 h after washing off CTZ
J Physiol. 2006 Mar 15;571(Pt 3):605-18.
rat hippocampal neurons
100 μM
Cyclothiazide significantly potentiated the AMPA-induced increase in intracellular free calcium ion concentration ([Ca2+]i), showing pronounced cell-to-cell variation.
Br J Pharmacol. 1998 Apr;123(7):1294-303.
Cyclothiazide/环噻嗪 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rats
Urethane-anaesthetized rats
Intracerebroventricular injection
5 μM (5μl)
Single injection, monitored for 3 hours
CTZ injection induced spontaneous epileptiform activity in the hippocampal CA1 region
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