• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.49-57
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• 1994

The binding properties of oxomemazine to muscarinic receptors using the ability of oxomemazine to inhibit $[^3H]QNB$ binding in membrane fractions of rat cerebrum and guinea pig ventricle and ileum were investigated. $[^3H]QNB$ bound to a single class of muscarinic receptors with a dissociation constant of approximately 60 pM in three tissue preparations. Pirenzepine and oxomemazine inhibited $[^3H]QNB$ binding in cerebrum with a Hill coefficient lower than unity, and the inhibition data were best described by a two-site model. The relative densities of the high $(M_1)\;and\;low\;(M_2)$ affinity sites for pirenzepine were 60 and 40%, with corresponding Ki values of 16 and 431 nM, and those $(O_H\;and\;O_L)$ for oxomemazine 40 and 60%, with corresponding Ki values of 80 and 1350 nM. However, the inhibition data of both drugs vs $[^3H]QNB$ in ventricle and ileum appeared to obey the law of mass-action (Hill coefficient close to 1). The apparent Ki values of pirenzepine were 850 and 250 nM, and those of oxomemazine 1460 and 570 nM in ventricle and ileum, respectively. Thus, oxomemazine like pirenzepine has high affinity for cerebrum, moderate affinity for ileum and low affinity for ventricle. These results suggest that oxomemazine could recognize the muscarinic receptor subtypes with a high affinity for the $M_1$ sites.

• Journal of Environmental Health Sciences
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• v.42 no.1
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• pp.27-33
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• 2016

Objectives: Alumina nanoparticles ($Al_2O_3$, Al-NPs) are used for various purposes, including as coating agents and paint additives. Their potential toxicity has raised concern for human health. This study focuses on exploring the toxic effects on the brain and kidneys caused by Al-NPs exposure in rats. Methods: The animals were orally administered Al-NPs at 10, 50 and 100 mg/kg body weight for 28 days following OECD TG 407. To determine the targeted toxicity of Al-NPs, histopathological examination and gene expression analysis were conducted on the rats. Results: The Al-NPs treatment induced kidney tubular dilatation. In the rat cerebrums, the expression levels of 126 genes experienced two-fold or greater increases in response to Al-NPs, including other genes encoding proteins involved in cell differentiation, transcription and signal transduction. In the rat kidneys, the expression levels of 152 genes also showed two-fold or greater increases in response to Al-NPs, including other genes encoding proteins involved in apoptosis, transcription and signal transduction. Conclusion: These results suggest that exposure to Al-NPs influences cellular signal pathways of kidney and cerebrum, and it can be a toxic indicators of nanometrials.

• Archives of Pharmacal Research
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• v.17 no.6
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• pp.443-451
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• 1994

The binding characteristics of pirenzepine and oxomemazine to muscarinic receptor were studied to evaluate the selectivity of oxomemazine for the muscarinic receptor subtypes in rat cerebral microsomes. Equililbrium dissociation constant $(K_D){\;}of{\;}(-)[^3H]$quinuclidinyl benzilate$([^3H)QNB)$ determined from saturation isotherms was 64-pM. Analysis of the pirenzepine inghibition curve of [$^3H$]QNB binding to cerebral microsome indicatd the presence of two receptor subtypes with high $(K_1 = 16 nM, M_1 receptor)$two receptor subypes with about 20-fold difference in the affinity for high $(k_1 = 84nM, {\;} O_H receptor){\;} and {\;}low{\;} (K_1{\;} ={\;} 1.65\muM, {\;} O_L receptor$) affinity sites. The percentage populations of $M_1{\;} and M_3$, /TEX> receptors to the total receptors were 61 : 39, and those of $O_H{\;} and{\;} O_L$ receptors 39 : 61, resepectively. Both pirenzepine and oxomemazine increaed the $K_D$ value for $[^3H]QNB$ without affecting the binding site concentrations and Hii coefficient for the $[^3H]QNB$ without affecting the binding site concentractions and Hill coefficient for the [$^{3}$H]QNB binding. Oxomemazine had a 10-fold higher affinity at $M_1$ receptors than at $M_3$ receptors, and pirenzepine a 8-fold higher affinity at $O_H$ receptors were of $O_H$ receptors and 71% of $M_3$ receptors. However, $M_3$for oxomemazine and $O_H$for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could be classified as a selective drug for $M_1$ receptors and also demonstrate that rat cerebral microsomes contain three different subtypes of $M_1{\;} M_3$ and the other site which is different from $M_1, {\;} M_2$, /TEX> receptors.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.70-78
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• 2009

Objectives : This study was aimed at examining the effects of the application of EA (electroacupuncture) at GV20 and LI4 in the early cerebral ischemia on the size of cerebral infarction, COX-2 and IL-6. Methods : For this experiment, 21, six-week-old male S-D (Sprague - Dawley) rats weighting 160g to 200g were selected and randomly classified into 3 groups, seven rats in each group. Brain ischemia was simulated using a modified Koizumi method which was performed on each rat. In the GV20 group, the GV20 of the SD rats was stimulated for thirty minutes with acupunctural electrode low frequency stimulator five hours after inducement of ischemia. For the LI4 group, the LI4 was stimulated as above, while for the Ischemia group, no stimulation was applied. Twenty-four hours after the experiment, stained cerebral tissues were examined and an immuno-histological test was done to examine inflammatory reaction Results : Out of the three groups, the LI4 group showed the smallest size of cerebral infarction and the Ischemia group showed the highest COX-2 (cyclooxygenase-2) expression value in the cortex of the cerebrum. In addition, the LI4 group showed the lowest COX-2 expression value in unknown putamen out of the three groups. Conclusions : We infer that EA, applied at LI4 and GV20 in early ischemia, is effective in delaying the expression of IL-6 (interleukin-6) and COX-2, the inflammatory agents manifested from stroke. In addition, application at LI4, rather than GV20, can lower the expression value of the inflammatory agents. Further, EA can be an effective way to block early inflammatory reaction in stroke.

• Journal of Pharmacopuncture
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• v.12 no.4
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• pp.5-32
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• 2009

Objectives: This study was performed to analyse single dose toxicity of pure melittin(Sweet Bee Venom-Sweet BV) extracted from the bee venom by utilizing protein isolation method of gel filtration. Methods: All experiments were conducted at Biotoxtech, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP). Six weeks old female Sprague-Dawley rats were chosen for the pilot study and determined 30㎎/㎏ which is 4285 times higher than the clinical application dosage as the high dosage, followed by 15 and 7.5㎎/㎏ as mid and lose dosage, respectively. Equal amount of excipient to the Sweet BV experiment groups was administered as the control group. Results: 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all groups, and higher occurrence in the higher dosage groups. Hyperemia and movement disorder diminished with elapsed time. 3. For the weight measurement, male groups showed larger reduction in weight in accordance with higher dosage. Female groups didn't s how significant changes. 4. To verify abnormalities of organs and tissues, cerebellum, cerebrum, liver, lung, kidney, and spinal nerves were removed and conducted histological observation with H-E staining. No abnormalities were detected in any of organs and tissues. 5. One female rat in the 30㎎/㎏ group had amputated toe near the administered area and histopathological finding was hemorrhage with inflammation. This is presumed as a secondary infection after the administration of Sweet BV. Conclusion: Above findings suggest Sweet BV is relatively s safe treatment medium. Further studies on the subject should be conducted to yield more concrete evidences.

• Journal of Ginseng Research
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• v.21 no.1
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• pp.53-60
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• 1997

The changes in aldehyde dehydrogenase(ALDH, E.C. 1.2.1.3.) activity in neurons and astrocytes isolated from rat brains were investigated after administration of ethanol and Korean red ginseng(Panax ginseng C.A. Meyer) saponln. The cerebral ALDH activity with acetaldehyde and Propionaldehyde was higher in the white matter than in the gray matter. However, using indole-3-a-cetaldehyde and 3,4-dihydroxyphenylacetaldehyde as substrates, there was no significant difference in activity between two regions in cerebrum. In ethanol treated group, ALDH activity with all the substrates in the gray and white matter was lower than in normal group. In ethanol-saponin treated group, the enzyme activity in the white matter remarkably Increased. The ALDH activity in neurons isolated from cerebral cortex in ethanol-treated group was lower than in normal group. In ethanol-saponin treated group, neuronal ALDH activity with propionaldehyde was significantly recovered but not with Indole-3-acetaldehyde. In astrocytes, although the ALDH activity with propionaldehyde in the ethanol-treated group was not changed as compared with normal group, considerable increase in activity was found in ethanol-saponin treated group. These results suggest that Korean red ginseng saponin may protect the neuronal functions from the toxic effects of acetaldehyde derived from ethanol by stimulation of ALDH activity in astrocytes surrounding nerve cells.

• Journal of Magnetics
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• v.19 no.1
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• pp.20-27
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• 2014

This study examined the relationships between protein expression and Poly ADP ribose polymerase in brain cell death in brains damaged by thrombotic stroke and treated with the Full Wave- Cockroft Walton (FWCW) method of Transcranial Magnetic Stimulation (TMS). The two-way switching element for TMS drove a half-bridge inverter of the current resonance of direct current voltage (+) and direct current voltage (-), and the experiment was conducted by stimulating the mice with thrombotic stroke through a range of pulses. Thrombotic stroke was caused of ligation of the common carotid artery of male SD mice, and blood reperfusion was conducted five minutes later. Protein expression was examined in immune reaction cells, which reacted to an antibody to Poly ADP ribose polymerase in the cerebrum cells, and western blotting. Observations of the PARP changes after thrombotic stroke showed that the number of Poly ADP ribose polymerase reactions were significantly lower (p < 0.05) in the group treated with TMS of the FWCW than the group with thrombotic stroke 24 hours after its onset. The application of FWCW-TMS helped prevent the necrosis of nerve cells and might prevent the brain damage that occurs as a result of thrombotic stroke, and improve the function recovery and disorder of brain cells.

• Archives of Pharmacal Research
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• v.26 no.9
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• pp.763-767
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• 2003

The differences in pharmacokinetic behavior and tissue distribution of verapamil and its enantiomers were investigated in rats. In high-performance liquid chromatographic method, an achiral ODS column (150 mm $\times$ 4.6 mm i.d.) with the mobile phase consisting of methanol-water (73:30, v/v) was used for the determination of the concentration for racemic verapamil, and a Chiralcel OJ column (250 mm$\times$4.6 mm i.d.) with the mixture of n-haxane-ethanol-triethylamine (85:15:0.2, v/v/v) as mobile phase was used to determine the concentrations of verapamil enantiomers. A fluorescence detector in the analytical system was set at excitation and emission wavelengths of 275 nm and 315 nm. The differences between enantiomers were apparent in the pharmacokinetics in rats. The area under the concentration-time curve (AUC) of S-(-) verapamil was higher than that of R-(+) verapamil. The half-distribution time ($T_{1/2(\alpha)}$) of S-(-) verapamil which distributing to tissue from blood was shorter than that of R-(+) verapamil, but the elimination half-time ($T_{1/2(\beta)}$) was longer in rat following oral administration of racemic verapamil. At 1.3 h after oral administration of racemic verapamil, however, there were no significant differences between enantiomers for the distributions in major tissues such as heart, cerebrum, cerebellum, liver, spleen and kidney.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.290-290
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• 1994

The binding characteristic of oxomemazine to muscarinic receptor in the cerebrum, heart, and ileum were compared to those of pirenzepine to investigate whether oxomemazine could classify the muscarinic receptor subtypes. 〔$^3$H〕Quinucl idinyl benzilate(QNB) identified a single class of muscarinic receptors with apparent K$\sub$D/ value of about 60 pM in three tissues. Analysis of the pirenzepine inhibition curve of 〔$^3$H〕QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki=16 nM, M$_1$-receptor) and low (Ki=400 nM, M$_2$-receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with high (Ki=84 nM, On-receptor) and low (Ki=1 4 ${\mu}$M, O$\sub$L/-receptor) affinity in rat cerebral microsome, The percentage population of the M$_1$-and M$_2$-receptors to the total receptors were 61 : 39, and those of the O$\^$H/- and O$\sub$L/-receptors 39 : 61, respectively, However, the Hill coefficients of these two drugs for the inhibition of 〔$^3$H〕QNB binding to the heart and ileum were close to unity which indicated that these drugs bound to a uniform population of receptors in these two tissues. The Ki values for the low affinity sites of pirenzepine and oxomemazine in the cerebrum were similar to those of these drugs in the heart ileum. Both pirenzepine and oxomemazine increased K$\sub$D/ value for 〔$^3$H〕QNB without affecting the binding sites concentration and Hill coefficient for the 〔$^3$H〕QNB binding. Oxomemazine had a 10-fold lower affinity at Ma-receptors than at M$_1$-receptors, and pirenzepine a 8-fold lower affinity at O$\sub$L/-receptors than OH-receptors. Analysis of the shal low competition curves of oxomemazine for the H$_1$ receptors and pirenzepine for the O$\sub$L/-receptors yielded that 69% of the M$_1$-receptors were of the O$\sub$H/-receptors and the remaining 31% of the O$\sub$L/-receptors, and that 29% of the O$\sub$L/-receptors were of the M$_1$-receptors and 71% of the M$_2$-receptors. However, M$_2$ for oxomemazine and O$\sub$H/ for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could discriminatethe muscarnic receptor subtypes and may subclassify the M$_1$-receptors into two subtypes.

• The Journal of Internal Korean Medicine
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• v.21 no.2
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• pp.319-327
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• 2000

To evaluate the effect of Bangpungdangkwi-eum extracts on reperfusion following the middle cerebral artery occulsion in Sprague Dawley rats, the neuron protection effect were investigated through examining the size of cerebral infarction, cerebral edema, and the morphologic change of neuron. The results were obtained as follows; 1. The size of cerabral infarction in sample group is significantly decreased compared with that in control group. Sample group has approximately 17% cerebral infarction parts induced by ischemia in cerebrum while control group has approximately 22%. 2. The volume of cerebral edema in sample group is significantly decreased compared with that in control group. The volumn in sample group is increased by approximately 4.4% compared with that in normal group while that in control group is increased by approximately 7.7%. 3. The optical microscopic examination reveals that the damage of neurons in the ischemic parts and CA1 and CA3 region of hippocampus in the same side of the ischemic parts was the most high and the damage in sample group is decreased compared with that in control group.