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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
Aim To observe the effects of borneol on the pharmacokinetics of carbamazepine(CBZ) and 10,11-epoxide carbamazepine(ECBZ) in rabbits.Methods After ig administration of bornol and CBZ,the CBZ and ECBZ were determined with HPLC,then the pharmacokinetic parameters were obtained with 3P87 program on computer.Results In the CBZ-borneol combination group,the pharmacokinetic parameters of CBZ,T_(12(ka)),T_(peak) and AUC were increased,while Ka and CL were decreased.The parameters of ECBZ,T_(12(ke)) and T_(peak) were increased,while Ke was decreased.The ratio of CSF to plasma of ECBZ at the time of 0.5,1,2 hour after ig was increased.Conclusion Borneol significantly improved the bioavailability of CBZ,inhibited the metabolism of CBZ,and enhanced the ECBZ passing through blood brain barrier.
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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.
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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.