• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.305-313
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• 1999

To explore whether $Cl^-$ channel blockers interact with the ATP-sensitive $K^+\;(K_{ATP})$ channel, I have examined the effect of two common $Cl^-$ channel blockers on the $K_{ATP}$ channel activity in isolated rat ventricular myocytes using patch clamp techniques. In inside-out patches, 4,4'-diisothio-cyanatostilbene- 2,2'-disulfonic acid (DIDS) and niflumic acid applied to bath solution inhibited the $K_{ATP}$ channel activity in a concentration-dependent manner with $IC_{50}$ of 0.24 and 927 ${\mu}M,$ respectively. The inhibitory action of DIDS was irreversible whereas that of niflumic acid was reversible. Furthermore, DIDS-induced block was not recovered despite exposure to ATP (1 mM). In cell-attached and inside-out patches, DIDS blocked the pinacidil- or 2,4-dinitrophenol (DNP)-induced $K_{ATP}$ channel openings. In contrast, niflumic acid did not block the pinacidil-induced $K_{ATP}$ channel openings in inside-out patches, but inhibited it in cell-attached patches. DIDS and niflumic acid produced additional block in the presence of ATP and did not affect current-voltage relationship and channel kinetics. All these results indicate that DIDS among $Cl^-$ channel blockers specifically blocks the cardiac $K_{ATP}$ channel.

• 대한화학회지
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• 제57권1호
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• pp.99-103
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• 2013

The present communication deals with the Pharmacophore modeling, 3D QSAR and docking analysis on series of Pyrimidine derivatives as potential calcium channel blockers. The computational studies showed hydrogen bond donor, hydrogen bond acceptor, and hydrophobic group are important features for calcium channel blocking activity. These studies showed that Pyrimidine scaffold can be utilized for designing of novel calcium channels blockers for CVS disorders.

• Biomolecules & Therapeutics
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• 제15권3호
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• pp.156-161
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• 2007

Rapid advances in pharmacogenomic research have provided important information to improve drug selection, to maximize drug efficacy, and to minimize drug adverse reaction. The SNPs that are the most abundant type of genetic variants have been proven as valid biomarkers to give information on the prediction of pharmacokinetic/pharmacodynamic properties of drugs based on genotype. In order to elucidate a correlation between SNPs of calcium channel encoding gene and adverse reactions of calcium channel blockers, we investigated SNPs in CACNA1C gene known as a binding site of calcium channel blocker. 96 patients with hypertension who had taken or are taking an antihypertensive drug, 1,4-dihydropyridine (DHP) were included for analysis. These patients were composed of 47 patients with adverse drug reactions (ADR) such as edema from calcium channel blockers and 49 patients without ADR as a control group. The exons encoding the drug binding sites were amplified by PCR using specific primers, and SNPs were analyzed by direct sequencing. We found that there was no SNP in the exons encoding DHP binding site, but four novel SNPs in the exon-intron junction region. However, four novel SNPs were not associated with the ADR of calcium channel blockers. In conclusion, this study showed that ADR from calcium channel blockers may not be caused by SNPs of the binding sites of calcium channel blockers in CACNA1C gene.

• 환경생물
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• 제19권2호
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• pp.107-112
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• 2001

조직센서는 극 미량의 Na+채널 차단 물질을 측정하기 위해 개발된 고감도 측정 장치로 해조류 내 $Na^+$ 채널 차단 생리활성물질의 양을 측정하기에 적합하였다. 본 연구는 해조류 내 $Na^+$ 채널 차단 생리활성물질의 존재를 학인 함으로써 해조류를 이용한 신성분 개발의 기초자료를 확보할 목적으로 수행되었다. 분석에 사용된 해조류는 총 92종으로 녹조류 13종, 갈조류 42종, 홍조류 37종으로, 주요 해조류 내 $Na^+$ 채널 차단 생리활성물질은 대체로 수온이 낮은 시기에 더 높은 값을 나타내었다. 이 결과로 볼 때 종특성과 환경이 생리활성물질의 농도에 영향을 주는 것으로 생각되고, 각 종에 대한 생활사 변화와 환경특성에 대한 상관성 연구가 필요한 것을 나타났다.

• Archives of Pharmacal Research
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• 제18권6호
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• pp.402-409
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• 1995

The effects of calcium channel blockers (CAB's) verapamil, diltiazem and nicardipine, on erythrocyte ghost membranes have been studied. Using the fluorospectroscopic method, it was observed that the fluidity of the inner layer of ghost membranes was increased with an increase of drug concentrations but did not any changes in the fluidity of the outer layer. These drugs showed protectuve effect against hypotonic hemolysis of erythrocytes. Thus, the expansion of surface area in response to corpuscular volume of erythrocytes in the presence of CAB's is seemed to play an important role in protecting hypotonic hemolysis of erythrocytes.

• 대한임상독성학회지
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• 제16권2호
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• pp.165-171
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• 2018

An overdose of antihypertensive agents, such calcium channel blockers (CCBs) and angiotensin II receptor blocker (ARBs), and the antihyperglycemic agent, metformin, leads to hypotension and lactic acidosis, respectively. A 40-year-old hypertensive and diabetic man with hyperlipidemia and a weight of 110 kg presented to the emergency room with vomiting, dizziness, and hypotension following an attempted drug overdose suicide with combined CCBs, ARBs, 3-hydroxy-3-methylglutaryl-coemzyme A reductase inhibitors, and metformins. A conventional medical treatment initially administered proved ineffective. The treatment was then changed to simultaneous extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), which was effective. This shows that simultaneous ECMO and CRRT can be an effective treatment protocol in cases of ineffective conventional medical therapy for hypotension and lactic acidosis due to an overdose of antihypertensive agents and metformin, respectively.

• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.55-62
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• 1998

${\alpha},\;{\beta}-Adrenergics$, and calcium channels were known to be related to inducing cardiac hypertrophy. Recently, it was reported that the cardiac renin-angiotensin system (RAS) was an important factor in ventricular hypertrophy. The present study was aimed to investigate the effects of ${\alpha},\;{\beta}-adrenergic$, and calcium channel blockers that might be involved in the regulation of cardiac RAS. The reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of renin gene in the perfused rat heart. Changes in angiotensin converting enzyme (ACE) activity and cyclic AMP (cAMP) content which were thought to play a role in inducing cardiac hypertrophy were measured in the perfused rat heart. The expression of renin gene was not only increased by isoproterenol with metoprolol-pretreatment but also increased by vasopressin treatment in the presence of calcium channel blocker, nifedipine or verapamil. Either prazosin alone or norepinephrine with prazosin-pretreatment significantly increased the ACE activity. However, isoproterenol with metoprolol-pretreatment significantly decreased the ACE activity. On the other hand, the ACE activity was not changed by vasopressin, nifedipine, or verapamil treatments. The content of cAMP was significantly increased by either isoproterenol or vasopressin treatment. According to these results, renin gene expression was associated with ${\beta}2$ - adrenoceptor and calcium channel. ACE activity was associated with ${\alpha}-\;and{\beta}2$ - adrenoceptor. In conclusion, ${\beta}2$ - adrenoceptor was important in cardiac renin gene expression and ACE activity and ${\alpha},\;{\beta}$ -adrenergic, and calcium channel blockers might be involved in the regulation of cardiac RAS in a complicated way.

• KSBB Journal
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• 제13권1호
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• pp.71-76
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• 1998

$Na^+$ 전극도 개구리 방광막으로 만들어진 조직센서를 이용하여 복어독 (TTX), 조개독 (STX), 마비성조개독 (PSP) 등의 $Na^{+}$ 챈널 차단물질을 측정하였다 본 연구는 연속적으로 $Na^{+}$ 챈널 차단물질을 측정할 수 있는 조직 센서를 이용하여 한국산 한방약의 재료와 건조 및 생김 (Porphyra yezoensis)의 $Na^+$ 챈널 차단물질의 존재여부를 측정하였다. 본 센서는 한방약 재료 및 해조류 (김 등)와 같이 현재 일반적으로 사용되고 있는 마우스법으로 측정이 불가능한 fg 단위의 매우 적은 양의 $Na^{+}$ 챈널 차단물질까지 측정이 가능하였다. 본 바이오센서는 $Na^{+}$ 챈널 차단물질의 모니터링 및 해양환경감시에 응용 가능하리라 기대된다.

• Bulletin of the Korean Chemical Society
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• 제32권spc8호
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• pp.3063-3073
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• 2011

The synthesis and biological evaluation of 1-heteroarylmethyl 1,4-diazepane derivatives as potential T-type calcium channel blockers is described. In this study, we have identified the compound 21i exhibiting the most potent T-type calcium channel blocking activity with $IC_{50}$ value of 0.20 ${\mu}M$, which is superior to that of mibefradil.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.119-127
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• 2016

Dihydropyridine (DHP) calcium channel blockers (CCBs) have been widely used to treat of several cardiovascular diseases. An excessive shortening of action potential duration (APD) due to the reduction of $Ca^{2+}$ channel current ($I_{Ca}$) might increase the risk of arrhythmia. In this study we investigated the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on the cardiac APD in rabbit Purkinje fibers, voltage-gated $K^+$ channel currents ($I_{Kr}$, $I_{Ks}$) and voltage-gated $Na^+$ channel current ($I_{Na}$). The concentration-dependent inhibition of $Ca^{2+}$ channel currents ($I_{Ca}$) was examined in rat cardiomyocytes; these CCBs have similar potency on $I_{Ca}$ channel blocking with $IC_{50}$ (the half-maximum inhibiting concentration) values of 0.142, 0.229, and 0.227 nM on NIC, ISR, and AML, respectively. However, ISR shortened both $APD_{50}$ and $APD_{90}$ already at $1{\mu}M$ whereas NIC and AML shortened $APD_{50}$ but not $APD_{90}$ up to $30{\mu}M$. According to ion channel studies, NIC and AML concentration-dependently inhibited $I_{Kr}$ and $I_{Ks}$ while ISR had only partial inhibitory effects (<50% at $30{\mu}M$). Inhibition of $I_{Na}$ was similarly observed in the three CCBs. Since the $I_{Kr}$ and $I_{Ks}$ mainly contribute to cardiac repolarization, their inhibition by NIC and AML could compensate for the AP shortening effects due to the block of $I_{Ca}$.