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Aim To establish a novel locomotor model based on accumulate peripheral active time percent(APATP)in ICR mice induced by pentobarbital sodium(PB)and diazepam.Methods Total distance, accumulate peripheral active time and accumulate peripheral time were aquired from video tracking system with computer, and APATP in all groups was fit and got correspondent parameters with Drugs Analysis System 2.0. Logarithm of area under the curve(lgAUC_(0-60)), minimum APATP(lgP_(min)), and half time of steady-state locomotor activity(T_(1/2α)) were ready for evaluation.Results APATP decreased with time increasing in all groups gradually, and PB 10 mg·kg~(-1) and PB 15 mg·kg~(-1) had similar tendency.PB 10 mg·kg~(-1) and PB 15 mg·kg~(-1) all decreased APATP significantly throughout the time course.APATP in all mice was fit to kinetics equation.Compared with norm group, PB 5 mg·kg~(-1) decreased three parameters slightly(all P >0.05), and PB 10 mg·kg~(-1) and PB 15 mg·kg~(-1) had similar tendency.PB 10 mg·kg~(-1) (all P <0.05) and PB 15 mg·kg~(-1) (P <0.01, P <0.01 and P >0.05)decreased parameters.Compared with PB 10 mg·kg~(-1) , PB 15 mg·kg~(-1) increased reversely(P >0.05, P <0.05 and P <0.05).lgAUC_(0-60) and lgPmin were both linar with total distance(r 2=1.0000 and r 2=0.9995, both P <0.01), T_(1/2α) also showed similar tendcency as well as total distance.Refering PB 10 mg·kg~(-1) as positive drugs and norm as negative control, diazepam 2 mg·kg~(-1) and 4 mg·kg~(-1) depressed all parameters significantly compared with norm group(all P <0.01) and were similar as PB 10 mg·kg~(-1) , which indicated that sedative effect of diazepam was the same as PB 10 mg·kg~(-1) .Conclusion Locomotor activity model based on APATP may be used to evaluate drug effects on lomocotor activity induced by sedative hypnotics.
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<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>
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Animals , Female , Male , Mice , Drug Interactions , Glutamates , Pharmacology , Hypnotics and Sedatives , Pharmacology , Mice, Inbred ICR , Motor Activity , Pentobarbital , PharmacologyABSTRACT
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.
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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