• The Korean Journal of Physiology
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• v.19 no.2
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• pp.101-111
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• 1985

Transient inward current (TI) was studied by the two micro-electrode voltage clamp technique in the sinoatrial node of the rabbit. The author confirmed that in $10^{-6}$ M ouabain TI was found in the SA node and investigated the effects of ions, $(Na^+,\;K^+,\;Ca^{2+})$, $\beta-agonist$ (isoprenaline), local anesthetics (quinidine, lidocaine) and Ca-blockers ($Co^{2+}$, verapamil, diltiazem) on the TI recorded during depolarizing voltage clamp pulses to -40 and -20 mV. The results obtained were as follows ; 1) $10^{-6}M$ ouabain increased the frequency of sinus action potential and decreased the amplitude, especially overshoot of action potential. TI was induced by the depolarizing voltage clamp Pulses and the magnitude of the slow inward current (isi) decreased and the time course was slowed by the same depolarizing pulses. 2) 30% $Na^{+}$ and 24mM $K^+$ decreased by $10^{-6}M$ ouabain and 6 mM $Ca^{2+}$ and $10^{-7}M$ isoprenaline increased TI, $i_{si}$ and current oscillations. 3) Quinidine $(5\times10^{-7}M)$ reduced TI and $i_{si}$ but lidocaine $(10^6\;-10^5M)$ didn't reduced or increase TI. Current oscillations increased and isi decreased by lidocaine. 4) Ca-blockers decreased the amplitude and the frequency of sinus action potential. TI and $i_{si}$ decreased significantly but were not abolished completely at the concentrations used in this experiment. Verapamil and diltiazem had inhibitory action on TI in $2\times10^{-7}M$ concentration and showed very slow recovery after wasting out with normal Tyrode solution.

• YAKHAK HOEJI
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• v.32 no.2
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• pp.101-111
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• 1988

$[^3H]$ Quinuclidinyl benzilate(QNB) binding assays were performed in the dog ventricular sarcolemma fraction enriched approx. 32-fold in sarcolemma compared to the starting homogenate to elucidate the effect of antihistaminics on cardiac muscarinic receptor. Chlorpheniramine(CHP) inhibited specific binding of $[^3H]$QNB and delayed the equilibrium binding. The rate constants at $37^{\circ}C$ for formation and dissociation of the QNB receptor complex were $0.38{\times}10^9\;M^{-1}$ and $1.6{\times}10^{-2}\;min^{-1}$, respectively. The mean value for the dissociation constant from the pairs of the rate constants was 43. 2 pM and this value was similar to the value(44.8pM) determined from Scatchard analysis. CHP decreased association rate constant, indicating increase in $K_D$ value. Decrease in affinity without affecting the binding site concentration$(B_{max})$ for $[^3H]$QNB binding by CHP was also demonstrated by Scatchard analysis. $K_i$ values for $H_i$-blockers that inhibited specific $[^3H]$QNB binding were $0.02{\sim}4.8{\mu}M$. Cimetidine with $K_i$ value of $230{\mu}M$, however, was ineffective in displacing $[^3H]$QNB binding at concentration of $50{\mu}M$. The Hill coefficient for $H_1$-blockers were about one. The results indicate that $H_1$-antihistaminics inhibit $[^3H]$ QNB binding by interaction with myocardiac muscarinic cholinergic receptor and anticholinergic side effects of these drugs are mainly due to this receptor blocking mechanism.

• Bulletin of the Korean Chemical Society
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• v.30 no.11
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• pp.2707-2712
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• 2009

5-$HT_{3}$ receptor;5-$HT_{3A}$ receptor channel activity;Novel 5-$HT_{3}$ receptor channel current blockers;Chlorophenyl substituted piperazinylethylaminomethylpyrazoles; The 5-$HT_{3A}$ receptors are one of ligand-gated ion channels and are known to be involved in visceral pain, anxiety, or anticancer agent-induced nausea and vomiting. In present study, we designed novel skeletons based on the developed 5-$HT_{3}$ receptor antagonists and evaluated their effects on 5-$HT_{3A}$ receptor channel currents ($I_{5-HT}$) of a series of pyrazole derivatives having N-chlorophenylpiperazine functionality (6-9). We found that most of N-p-chlorophenyl substituted piperazinyl-pyrazole derivatives (7b, 7c, 7e and 7h) exhibited the high potency for the inhibition of $I_{5-HT}$, whereas the compound without chloride (6) or with m-chlorophenyl group (a serious of 8 and 9) showed the low potency. These result indicate that p-chlorophenyl group is might play an important role for increasing the inhibitory potency on $I_{5-HT}$.

• Journal of Radiation Industry
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• v.10 no.4
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• pp.181-187
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• 2016

Selective ${\beta}_1$-agonist and antagonists are used for the treatment of cardiac diseases including congestive heart failure, angina pectoris and arrhythmia. Selective ${\beta}_1$-antagonists including nebivolol have high binding affinity on ${\beta}_1$-adrenergic receptor, not ${\beta}_2$-receptor mainly expressed in smooth muscle. Nebivolol is one of most selective ${\beta}_1$-blockers in clinically used ${\beta}_1$-blockers including atenolol and bisoprolol. We tried to develop clinically useful cardiac PET tracers using a selective ${\beta}_1$-blocker. Nebivolol is $C_2$-symmetric and has two chromane moiety with a secondary amino alcohol and aromatic fluorine. We adopted the general synthetic strategy using epoxide ring opening reaction. Unlike formal synthesis of nebivolol, we prepared two chromane building blocks with fluorine and iodine which was transformed to diaryliodonium salt for labelling of $^{18}F$. Two epoxide building blocks were readily prepared from commercially available chromene carboxylic acids (1, 8). Then, the amino alcohol building block (15) was prepared by ammonolysis of epoxide (14) followed by coupling reaction with the other building block, epoxide (7). Diaryliodonium salt, a precursor for $^{18}F$-aromatic substitution, was synthesized in moderate yield which was readily subjected to $^{18}F$-aromatic substitution to give $^{18}F$-labelled nebivolol.

• Journal of Biomedical and Translational Research
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• v.19 no.4
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• pp.86-91
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• 2018

Angiotensin receptor blockers, such as telmisartan, are considered effective in the treatment of hypertension and proteinuria due to chronic kidney disease (CKD) in cats. It selectively blocks the $AT_1$ receptor and does not affect the $AT_2$ receptor, thus effectively blocking the activity of the renin angiotensin aldosterone system. This study aims to compare over time the changes in various indicators, including systemic hypertension and proteinuria, before and after the administration of telmisartan in cats with CKD. Decrease in blood pressure (BP) (p<0.001) and urine protein to creatinine (UP/C) ratio (p<0.001) were found to be statistically significant over time after the administration of telmisartan. BP and the UP/C ratio were $160{\pm} 22.2$ and $0.50{\pm}0.647$ before telmisartan administration (Day 0), $150{\pm}21.0$ and $0.27{\pm}0.487$ on the 30th day (Day 30), $150{\pm}17.0$ and $0.25{\pm}0.376$ on the 60th day (Day 60), and $140{\pm}17.8$ and $0.15{\pm}0.233$ on the 90th day (Day 90) after administration, respectively. BP and UP/C were statistically significantly lower in cats with CKD over time at each time point from Day 0 to Day 90 at 30 day intervals. Especially after 90 days of telmisartan administration, the improvement of BP and UP/C were estimated to be about 20 mmHg and 0.35, respectively. In conclusion, the oral administration of telmisartan to cats with CKD is effective in improving BP and proteinuria, which has a positive effect on long-term survival in cats with CKD.

• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.82.1-82.13
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• 2018

Objective: The impact of beta blockers (BBs) on survival outcomes in ovarian cancer was investigated. Methods: By using Korean National Health Insurance Service Data, Cox proportional hazards regression was performed to analyze hazard ratios (HRs) with 95% confidence intervals (CIs) adjusting for confounding factors. Results: Among 866 eligible patients, 206 (23.8%) were BB users and 660 (76.2%) were non-users. Among the 206 BB users, 151 (73.3%) were non-selective beta blocker (NSBB) users and 105 (51.0%) were selective beta blocker (SBB) users. BB use in patients aged ${\geq}60$ years, longer duration use (${\geq}1$ year), in patients with Charlson Comorbidity Index (CCI) ${\geq}3$, and in cardiovascular disease including hypertension was associated with better survival outcome. These findings were observed in both NSBB and SBB. When duration of medication was analyzed based on number of days, NSBB (${\geq}180$ days) was associated with improved overall survival (OS) with a relatively shorter period of use compared to SBB (${\geq}720$ days). In multivariate Cox proportional hazards model, longer duration of BB medication (${\geq}1$ year) was an independent favorable prognostic factor for both OS and disease-specific survival in ovarian cancer patients. Conclusion: In our nationwide population-based cohort study, BB use was associated with better survival outcomes in ovarian cancer in cases of long term duration of use, in older patients, and in cardiovascular and/or other underlying disease (CCI ${\geq}3$).

• Korean Journal of Clinical Pharmacy
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• v.30 no.4
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• pp.259-263
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• 2020

Background: Dual-type calcium channel blockers (CCBs), such as efonidipine and cilnidipine, are renoprotective drugs that reportedly reduce proteinuria by dilating afferent and efferent arterioles of the glomerulus. However, studies comparing the effect of dual-type CCB on proteinuria have not been conducted. Therefore, we aimed to compare the effect of dual-type CCB (efonidipine and cilnidipine) usage patterns in hypertensive patients with chronic kidney disease (CKD). Methods: This single-center, retrospective study included 53 patients with CKD who 1) initiated efonidipine or cilnidipine treatment while on a renin-angiotensin system inhibitor and 2) had received efonidipine or cilnidipine for at least one year. We compared usage patterns between the efonidipine and cilnidipine groups during the one-year period and analyzed the following outcomes: urinary protein-to-creatinine ratio, blood pressure, and serum creatinine. Results: The study included 25 patients in the efonidipine group and 28 patients in the cilnidipine group. In both groups, blood pressure and urinary protein-to-creatinine ratios tended to decrease; however, the change during each interval was not significant. Conclusions: In patients with CKD who were on renin-angiotensin system inhibitor therapy, the addition of a dual-type CCB (i.e., efonidipine or cilnidipine) tended to reduce proteinuria; however, the change during each interval was not significant.

• Tuberculosis and Respiratory Diseases
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• v.87 no.2
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• pp.185-193
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• 2024

Background: The mechanisms leading to lung fibrosis are still under investigation. This study aimed to demonstrate whether antacids could prevent the development of interstitial lung disease (ILD). Methods: This population-based longitudinal cohort study was conducted between January 2006 and December 2010 in South Korea. Eligible subjects were ≥40 years of age, exposed to proton pump inhibitors (PPI)±histamine-2 receptor antagonists (H-2 blockers) or H-2 blockers only, and had no history of ILD between 2004 and 2005. Exposure to antacids was defined as the administration of either PPI or H-2 receptor antagonists for >14 days, whereas underexposure was defined as antacid treatment administered for less than 14 days. Newly developed ILDs, including idiopathic pulmonary fibrosis (IPF), were counted during the 5-year observation period. The association between antacid exposure and ILD development was evaluated using adjusted Cox regression models with variables, such as age, sex, smoking history, and comorbidities. Results: The incidence rates of ILD with/without antacid use were 43.2 and 33.8/100,000 person-years, respectively and those of IPF were 14.9 and 22.9/100,000 person-years, respectively. In multivariable analysis, exposure to antacid before the diagnosis of ILD was independently associated with a reduced development of ILD (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.45 to 0.71; p<0.001), while antacid exposure was not associated with development of IPF (HR, 0.88; 95% CI, 0.72 to 1.09; p=0.06). Conclusion: Antacid exposure may be independently associated with a decreased risk of ILD development.

• Transactions of Materials Processing
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• v.7 no.3
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• pp.298-305
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• 1998

In hot forging the blocker is a transient shape between the buster and the finisher, In general as the finisher shape becomes complicated the blocker design becomes quite difficult. In the present study an expert system is developed for the blocker die design of axisymmetric hot steel forging. It is a rule based system written in Fortran and AutoLISP operating on a personal computer. In this paper the major rules considered in the system are summarized and several blockers designed by the system are discussed with results of rigid viscoplastic finite element analysis.

• Bulletin of the Korean Chemical Society
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• v.32 no.4
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• pp.1237-1240
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• 2011

In this study, we have developed a ligand-based in-silico prediction model to classify chemical structures into hERG blockers using Bayesian and random forest modeling methods. These models were built based on patch clamp experimental results. The findings presented in this work indicate that Laplacian-modified naive Bayesian classification with diverse selection is useful for predicting hERG inhibitors when a large data set is not obtained.