Theanine affects sedative effect of pentobarbital sodium in ICR mice / 中国中药杂志

<p><b>OBJECTIVE</b>To evaluate the effects of theanine on sedative effects induced by pentobarbital sodium.</p><p><b>METHOD</b>The locomotor activities of ICR mice induced by theanine (0.25, 0.5, 1.0, 2.0, 4.0 g x kg(-1)), pentobarbital sodium (5, 10 mg x kg(-1)) or the combination of both were determined with video-tracking system, and a novel index: Peripheral active time Peripheral time (PATP) was established. Hypnosis effect of combination of both was tested with right-reflex disappearance.</p><p><b>RESULT</b>Compared with normal saline (74.52 +/- 20.4)%, theanine alone decreased this PATP in dose-dependent manner from (62.03 +/- 21.11)%, (56.44 +/- 21.69)%, (31.13 +/- 17.2)%, (25.06 +/- 10.03)% to (17.21 +/- 7.43)% (P>0.05, P<0.05, P<0.01, P<0.01 and P<0.01, respectively). Compared with pentobarbital sodium (5 mg x kg(-1)), between 0.25 g x kg(-1) and 1.0 g x kg(-1) theanine combined with that decreased peripheral PATP from (28.30 +/- 17.57)%, (30.64 +/- 17.21)% to (24.28 +/- 9.59)% (all P<0.01), and increased by 2.0 g x kg(-1) reversely (61.95 +/- 19.39)%. Compared with normal saline, pentobarbital sodium (10 mg x kg(-1)) and the combination with theanine decreased significantly PATP (all P<0.01). Compared with pentobarbital sodium (10 mg x kg(-1)), 0.25 g x kg(-1) theanine combined with that increased PATP [(25.37 +/- 13.68)% vs (10.08 +/- 7.98)%, P<0.01)] and 0.5 g x kg(-1), 1.0 g x kg(-1) theanine could depresse that increase [(14.56 +/-10.10)%, (8.24 +/- 4.08)% vs (10.08 +/- 7.98)%]. Total distance and peripheral active time showed the same or similar tendency in theanine alone or combination with pentobarbital sodium . Theanine enchanced hypnosis effect of pentobarbital sodium in dose-dependent manner.</p><p><b>CONCLUSION</b>Theanine can affect the sedative effect of low dose pentobarbital sodium in bidirectional action style but not change the hypnosis effect.</p>

Relation between modulation of the N-methyl-D-aspartate receptor and cyanide-induced neurotoxicity / 中国临床药理学与治疗学

Cyanide can activate the N-methyl-D-aspartate (NMDA) receptor by two approaches directly and indirectly. Firstly cyanide-induced depletion of energy is associated with the activation of NMDA receptors indirectly by increasing extracellular glutamate (Glu) and affecting cytosolic Ca 2+ homeostatic mechanisms. Secondly most likely as a conditioner of the NMDA receptor, cyanide enhances NMDA receptors responses by modulating redox sites of cysteine residue located in the subunit NR 1 or NR 2 of the NMDA receptor. NMDA receptor-induced neurotoxicity, initiated by the direct or indirect activation of NMDA receptor, leads to neuronal injury, apoptosis or necrosis finally. Therefore, it is believed that the activation of the NMDA receptor is presumably the key event in the mechanism of cyanide-induced neuronal injures.

Relationship between glutamate transporter, glutamate/cysteine transporter and neurotoxicity induced by glutamate / 中国临床药理学与治疗学

This paper introduces the relationship between glutamate transporter, glutamate/cysteine transporter and neurotoxicity induced by glutamate. Under pathologic conditions, glutamate transporters release glutamate to activate glutamate receptors, and inhibit the uptake of glutamate/cysteine transporters, which induces downstream changes. Among these changes oxygen derived free radidicals affects the function of glutamate transporter and enhances the neurotoxicity of glutamate. All these can lead to neurocyte death. Glutamate transporters release glutamate to inhibit the uptake of glutamate/cysteine transpoter and activate glutamate receptor. The inhibition of glutamate/cysteine transpoter affects the function of glutamate transporter. Two transporters interaction and the downstream changes lead to neurocytes death.

Antidotal effect of N-acetylcysteine on acute poisoning with sodium cyanide / 中国临床药理学与治疗学

AIM: To study the antidotal effect of N-acetylcysteine(NAC) on acute poisoning with sodium cyanide(NaCN).METHODS:After intraperitoneal(ip) injected of four sulphydryl compounds respectively,the mice which were acutely poisoned by NaCN were observed of the behavioral change,convulsion number and mortality rate(within 72 h).The median lethal dose(LD_(50)) of acutely poisoned mice was detected in NaCN group and NAC protection group.1 min after mice were poisoned by NaCN,the mice were divided into three groups:the first was ip normal saline(NS),the second was ip NAC in combination with sodium thiosulfate(Na_2S_2O_3),the third was ip sodium nitrite(NaNO_2) in combination with Na_2S_2O_3.Then the behavioral change,convulsion number and mortality rate(within 72 h)were observed,recorded,and compared the differences between the mice groups.RESULT: All of the four sulphydryl compounds had protecting effect on acutely NaCN poisoned mice,among them NAC had most prominent effect(P

Effects of combination of ketamine and N-acetylcysteine on brain damage following cerebral ischemia /reperfusion in mice / 中国临床药理学与治疗学

AIM: To evaluate the effects of the combination of ketamine (KT) and N-acetylcysteine (NAC) on damage following cerebral ischemia/reperfusion in ICR mice. METHODS: Male ICR mice were randomly divided into seven groups: Sham group, NS (saline 0.1 ml?kg -1 ) group, KT (15 mg?kg -1 ) group, NAC (75 mg?kg -1 ) group, NAC+KT (75+15 mg?kg -1 ) group. (1) ICR mice underwent two hours cerebral ischemia by transient right middle cerebral artery occlusion (tMCAO) and followed 6 h and 24 h reperfusion. Then brains were prepared for the determination of the infarction volume. Before the death, neurological deficits were scored. (2) ICR mice subjected to five minutes ischemia by two common carotid arteries occlusion (2-VO) and followed 0.5 , 2 and 6 h reperfusion. Brains were prepared for the determination of the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of MDA. RESULTS: (1) tMCAO produced severe neurological deficits, decreased the average score and brought about large infarction volume. KT, NAC showed the improvement of the average score and reduced infarction volume to some extent, and KT+NAC improved significantly. (2) The content of the MDA, the activities of GSH-Px and SOD in 2-VO mice deteriorated sharply, KT, NAC reduced the content of the MDA, enhanced the activities of GSH-Px and SOD, NAC+KT significantly ameliorated the levels of MDA, increased the activity of SOD and GSH-Px. CONCLUSION: The damage of cerebral ischemia/reperfusion leads to the decrease of neurological score, the increase of infarction volume, the reduction of activities of SOD and GSH-Px and the elevation of MDA. KT and NAC partly relieve the damage, and NAC and KT in combination attenuates the damage more effectively.