• 약학회지
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• 제31권5호
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• pp.322-329
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• 1987

A rapid and sensitive spectrophotometric method has been developed for quantitation of some phenothiazine derivatives (PTZDS). The method depends on the formation of insoluble yellow complexes between PTZDS and picric acid (PCA) in aqueous layer. These complexes are quantitatively extracted from aqueous phase into chloroform. The binding ratio of PTZDS-PCA complexes were presumed as PTZDS-1 to PCA-1 by means of mole ratio and continuous variation methods. The complexes are stable for more than 24hours in chloroform layer at room temperature. Most of compounds associated with pharmaceutical preparation of PTZDS do not interfere with this method. However, chlorpheniramine and diphenhydramine interfere with the riaethod. The binding state of PTZDS-PCA complexes were presumed by IR and $^1$H-NMR spectra as intermolecular hydrogen bonding.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.275-279
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• 1993

Single oral administration to SD rats of both sexes were performed to investigate the acute toxicity of two new cough and cold remedies, WHS-1 and WHS-2. WHS-1 is composed of acetaminophen, chlorpheniramine maleate, cloperastine hydrochloride, dl-methylephedrine hydrochloride, caffein anhydrous, thiamine hydrochloride, riboflavin and serratiopeptidase. WHS-2 is composed of similar formula except that thiamine hydrochloride and riboflavin is not added. The results were as follows. $LD_{50}$ values of WHS-1 were 4295.5 mg/kg for males and 4606.3 mg/kg for females, and $LD_{50}$ values of WHS-2 were 3236.7 mg/kg for males and 4360.5 mg/kg for females. Death occurred within 2~3 hours after administration at doses up to 2900 mg/kg in WHS-1 and 2500 mg/kg in WHS-2, the main cause of deaths seemed to be respiratory disturbance. General symptoms included decreased motor activity, salivation and loss of consciousness which were commonly observed in all dead animals treated with WHS-1 and WHS-2. No significant gross finding and body weight changes were observed at any dose level in the groups treated with WHS-1 and WHS-2.

• 대한수의학회지
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• 제33권1호
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• pp.71-80
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• 1993

The central nervous system depressant effect of xylazine and xylazine-ketamine was studied in chicken and mice. Intraperitoneal injection of xylazine(1~30 mg/kg) and xylazine(1~30 mg/kg)-ketamine(100 mg/kg) induced a loss of the righting reflex in chicken and mice, respectively. These effects of xylazine were dose-dependent. The results obtained were as follows; 1. The effect of xylazine-induced depression was antagonized by adrenergic antagonists having ${\alpha}_2$-blocking activity(yohimbine, tolazoline, piperoxan and phentolamine). 2. Yohimbine was most effective in the reduction of the CNS depression by xylazine. 3. Phenoxybenzamine and prazosin did not reduced CNS depression by xylazine in both species. 4. Labetalol (${\alpha}_1$, ${\beta}_1$-adrenergic antagonist) and propranolol(${\beta}$-adrenergic blocking agent) were not effective in reducing xylazine induced depression. 5. Cholinergic blocking agents (atropine and mecamylamine), a dopaminergic antagonist (Haloperidol), a histamine $H_1$-antagonist(chlorpheniramine), a histamine $H_2$-antagonist(cimetidine), a serotonergic-histamine $H_1$ antagonist(cyproheptadine) were not effective in reducing xylazine-induced depression. 6. Xylazine-induced depression is mediated by ${\alpha}_2$-adrenergic receptors and appears not to be involved in cholinergic, dopaminergic, serotonergic or histaminergic pathways.

• The Korean Journal of Physiology
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• 제17권2호
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• pp.109-117
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• 1983

The effects of histamine on contraction of rabbit taenia coli were studied. The results obtained were as follows: 1) The contractile response to histamine was appeared at the concentration of $10^{-7}M$ and increased in a dose-dependent manner to the concentration of $10^{-4}M$. 2) The magnitude of the histamine-induced contractile response was declined during short-term exposure in rabbit taenia coli. After 40-min exposure to histamine, the contractile response did not altered. 3) Histamine-induced contraction was not influenced by hexamethonium$(10^{-4}M)$, propranolol$(10^{-4}M)$ and phenoxybenzamine$(10^{-6}M)$. 4) $H_1-receptor$ blockade such as chlorpheniramine$(10^{-6}M)$ and pyrilamine$(10^{-6}M)$ completely abolished the response of the taenia coli to exogenous histamine, while $H_2-receptor$ blockade (cimetidine, $10^{-6}M$) did not alter. 5) After the treatment of verapamil the histamine-induced contraction was significantly inhibited, but in the treatment of 2 mM $La^{3+}$ it was not influenced. 6) In the absence of $Ca^{2+}$, histamine induced contraction in the different manner of acetylcholine. When taenia coli war treated with atropine$(10^{-6}M)$ which was completely blocked the contraction by acetylcholine$(10^{-4}M)$, histamine-induced contraction was not altered. These results suggest that in the rabbit taenia coli exogenous histamine induced contraction through $H_1$-receptor, but not through the mechanism of acetylcholine.

• 대한수의학회지
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• 제24권1호
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• pp.17-23
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• 1984

To validate the physiological properties of the histamine receptors of ileal smooth muscle in dog, the effects of adrenergic-, cholineric-, and H-receptor antagonists on the responses of ileal smooth muscle strips to histamine were investigated. The results were summarized as follows; 1. Histamine caused the contraction of ileal smooth muscle and the contractile responses were increased between the concentration of histamine $10^{-7}M$ and $10^{-5}M$ with dose-dependent manner in dog. 2. The shorter the treatment interval of histamine, the lower the contractile activity until the treatment interval extended to 40 minutes. 3. The contractile response induced by histamine was completely blocked by the pre treatment with a $H_1$-receptor blocker, chlorpheniramine and not by the pretreatment with a $H_2$-receptor blockers cimetidine. 4. The contractile response induced by histamine was not blocked by the pretreatment with a cholinergic receptor blocker, atropine. 5. The contractile response induced by histamine was not blocked by the pretreatment with an ${\alpha}$-adrenergic receptor blocker, phenoxybenzamine, or a ${\beta}$-adrenergic receptor blocker, propranolol. From these results, it was suggested that the contraction induced by histamine was elicited through $H_1$-receptor on the ileal smooth muscle in dog.

• 한국임상수의학회지
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• 제40권4호
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• pp.288-293
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• 2023

A 11-year-old neutered male Maltese dog was vaccinated with a rabies vaccine (Rabisin^®, Boehringer Ingelheim International GmbH, Germany) subcutaneously at a local animal hospital. One hour after vaccination, purpura with edema was observed at the injection site and severe thrombocytopenia (0 K/μL) was noted on a complete blood count (CBC). No specific findings were found in serum chemistry, electrolyte, blood gas analysis, and coagulation tests. The patient was hospitalized and administered antihemorrhagic agents (vitamin K, desmopressin), antihistamines (chlorpheniramine) and corticosteroids (methylprednisolone sodium succinate). On a repeat CBC, mild anemia had developed, thrombocytopenia was still noted, and autoagglutination was observed on a saline agglutination test (SAT). A polymerase chain reaction panel for infectious agents (e.g., Babesia spp.) was negative. The diagnosis was secondary immune-mediated thrombocytopenia (IMT) with immune-mediated hemolytic anemia (IMHA) associated with vaccination. Therefore, the immunosuppressants (prednisolone, and mycophenolate mofetil) were administered. Six days after drug administration, new lesion was not observed, and the previous lesions were significantly improved. It gradually improved and 4 weeks after hematocrit and platelet recovered to normal levels. It was maintained for 6 months without recurrence of related symptoms. Based on patient's history and test results, the patient was diagnosed with Evans' syndrome associated with rabies vaccine.

• 한국임상약학회지
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• 제25권4호
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• pp.254-263
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• 2015

Objectives: The present study assessed the prevalence of the potentially inappropriate medication (PIM) use in Korean elderly patients with Parkinson's disease. In addition, this study examined risk factors that affect PIM use. Method: A retrospective, observational study was conducted using Korean National Health Insurance claims database of 2009. PIM use in Parkinson's disease patients aged 65 years or older was examined based on 2012 Beers Criteria. Multivariable logistic regression was conducted to identify risk factors for PIM use. Results: Among 5,277 elderly patients with Parkinson's disease, 88.9% of patients used PIM(s) at least once. The average number of PIM items used per patient was 4.2. PIM use ratio, the proportion of total amount of PIMs to all medications per patient, was 12.6%. Frequently used PIM therapeutic classes were benzodiazepines (32.7%), first-generation antihistamines (19.2%), and prokinetics (17.5%). Individual PIMs most commonly used included chlorpheniramine (11.4%), levosulpiride (10.9%), diazepam (9.0%), and alprazolam (7.6%). Women (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.11-1.16), medical aid (OR 1.18, 95% CI 1.15-1.21), and long-term facilities (OR 2.43, 95% CI 2.22-2.65) were shown to be risk factors associated with PIM use. Of particular, wide variation in PIM use was associated with the types of healthcare facility. Conclusion: The PIM prevalence was very high in elderly Parkinson's disease patients. Nationally effective and systematic efforts to identify and prevent PIM use should be made to ensure patient safety and to improve quality of care in the elderly.

• 대한약리학회지
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• 제18권1호
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• pp.17-22
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• 1982

Zizyphus seed(Zizyphus vulgaris Lamark var. Spinosus Bunge) has long been used as hypnotics and sedatives in oriental medicine, and it is reported that the Zizyphus seed elicited a variety of pharmacologic actions besides CNS depression. Present study was undertaken to investigate the effects of Zizyphus seed on the central nervous system and on the blood pressure. The effect of Zizyphus seed on the central nervous system was measured by the influence of thiopental sleeping time and by inhibition of chemical convulsion (strychnine and pentylenetetrazol induced). Blood pressure changes by Zizyphus extract and its mode of action were investigated. The ground Zizyphus seed was extracted with hexane and methanol, consecutively and the supernatants were discarded. The precipitate was re-extracted with distilled water and the supernatant was evaporated to a dark-brownish sticky liquid, which was used as Zizyphus seed extract in this study after dissolving in saline prior to experiment. The results are as follows. 1) Zizyphus seed extract caused marked prolongation of the thiopental sleeping time in mice. 2) The chemical convulsion by strychnine and pentylenetetrazol, and the mortality by them in chicks were not affected by pretreatment of Zizyphus seed extract. 3) Zizyphus seed extract produced transient fall of blood pressure in the cat, and this hypotentive effect was blocked partially by atropine but not affected by bilateral vagotomy and/or hexamethonium, nor propranolol and, chlorpheniramine and/or cimetidine. With the above results, it may be suggested that the water extract of Zizyphus seeds contains components producing CNS depression and hypotension. Furthermore it is felt that the cholinergic effect, but not the adrenergic or histaminergic, is partly responsible for the hypotensive effect of Zizyphus seed extract.

• Archives of Pharmacal Research
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• 제14권2호
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• pp.181-187
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• 1991

The muscarinic antagonist 1-[benzilic 4, 4'-$[^3H]$ QUINUCLIDINYL BENZILATE $([^3H]$ QNB) bound to a single class of muscarinic receptors with high affinity in rabbit ileal membranes. The $K_D\;and\;B_{ max}$ values for $([^3H]$ QNB calculated from analysis of saturation isotherms were 52.5 pM AND 154 fmol/mg, respectively. Chlopheniramine (CHP), histamine $H_1$ blocker, increased $K_D$ vlue for $([^3H]$QNB without affecting the binding site concentrations and Hill coefficient. The $K_i$ value of CHP for inhibition of $([^3H]$QNB binding in ileal membranes was 1.44\mu{M}$ and the pseudo-Hill coefficient for CHP was close to unit. In the functional assay carbachol, muscarinic agonist, increased the contractile force of ileum with $ED_{50}$ value of $0.11\mu{M}$. CHP caused the rightward shift of the dose-response curve to carbachol. The $pA_2$ value of CHP determined from Schild analysis of carbacholinduced contraction was 5.77 and the slope was unity indicating competitive antagonism with carbachol. The dissociation constant $(K_i)$ of CHP obtained in competitive experiments with $([^3H]$ QNB was similar to the $K_A$ value (1.69 \mu{M)}$ of CHP as inhibitor of carbachol induced contraction in rabbit ileum. This result suggest that the binding of $H_i$ blocker. CHP, vs $([^3H]$QNB to muscarinic receptors in ileal membranes represents an interaction with a receptor of physiological relevance.

• 생약학회지
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• 제1권3호
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• pp.93-99
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• 1970

There have been reported by several workers for the isolation and determination of the amine derivatives as Metbylephedrine Hydrochloride and Ephedrine Hydrochloride adopting neutralization method, steam distillation method, non-aqous titration method, ion-exchange resin method, titration method after acetylation, colorimetric method, gravimetric method, iodine titration method and gas chromatography. Those methods mentioned in above, can be practically applied for the sample which is not mixed one mith the other amine compounds. Presently, it has not shown on the isolative determination of the mixed sample of amine derivatives. In this paper, it is discussed on the isolative determination of Methylephedrine Hydrochloride as the tertiary amine compound and Ephedrine Hydrochloride as the secondary amine compound. According to the results of the experiment, it could be summarized as follows: 1. There is no time-variation on the color reaction of Methylephedrine Hydrochloride and Ephedrine Hydrochloride with the color reagent, bromcresolgreen. And Methylephedrine Hydrochloride and Ephedrine Hydrochloride, respectively, can be determined spectrophotometrically by means oft his color reaction. 2. For the isolation of Methylephedrine Hydrochloride and Ephedrine Hydrochloride from the mixed sample, Methylephedrine Hydrochloride can be eluted by chloroform, while Ephedrine Hydrochloride by the mixed solvent of chloroform and ethylalcohol (2:1), from the celite column adsorbed at pH6.4 followed by extraction with ether undersodium hydroxide alkali re action. 3. When the sample is mixed with quinine hydrochloride, dihydrocodeine bitartate, and noscapine, these mixed compounds can be eliminated by means of stram distillation. 4. When the sample is mixed with chlorpheniramine maleate, dextromethorphan hydrobromide and diphenhydramine hydrochloride, the mixed compounds can be eliminated by means of steam distillation and celite adsorption column chromatography, In conclusion, the isolative determination method for Methylephedrine Hydrochloride and Ephedrine Hydrochloride studied in this paper, indicates with the excellent reproducibility and accuracy.