• Childhood Kidney Diseases
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• v.3 no.2
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• pp.170-179
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• 1999

Purpose: To evaluate whether or not sodium restriction had its own beneficial effect and increased the efficiency of the anti-hypertensive drugs on the progression of renal failure. Methods: We studied using the excision remnant kidney model. Treatment groups were as follows: 5/6 nephrectomy and a 0.49% (normal-high) sodium diet (NN); 5/6 nephrectomy and a 0.25% (normal-low) sodium diet (LN); 5/6 nephrectomy, a 0.49% sodium diet and enalapril (NNE); 5/6 nephrectomy, a 0.49% sodium diet and nicardipine (NNN); 5/6 nephrectomy, a 0.25% sodium diet and enalapril (LNE); 5/6 nephrectomy, a 0.25% sodium diet and nicardipine (LNN). Both diets were isocaloric and had the same content of protein, phosphorus and calcium. Proteinuria, remnant kidney weight, mesangial expansion scores, and glomerular volume were assessed. Results: Blood pressure tended to be lower in LN compared to NN (P<0.05). NN developed progressive hypertension. LNE, LU, NNE, and NNN reduced blood pressure. LNE, LNN, NNE, NNN, and LN had significantly less proteinuria than NN at 16 weeks (P<0.05). At 24 weeks, LN developed proteinuria (82 mg/day), which were lessened in LNE (54 mg/day) and not lessened in LNN (76 mg/day). Mesangial expansion scores were significantly less in LN rats compared to those in NN rats. Glomerular volumes at 24 weeks in LN rats were significantly less compared to those at 16 weeks in NN rats. Mesangial expansion scores and glomerular volumes at 4, weeks, 12 weeks, and 24 weeks were not different among LN, LNE, and LNN groups. Conclusion: Dietary salt restriction lessens renal damage, at least in part, by inhibiting compensatory renal growth and reducing blood pressure. Enalapril was particularly successful in reducing proteinuria and glomerular injury when combined with dietary salt restriction.

• Archives of Pharmacal Research
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• v.14 no.3
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• pp.271-278
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• 1991

To investigate further whether the effects of the dihydropyridine (DHP) drugs on calcium channels are related to those of these drugs on muscarinic receptors, the binding characteristics of the DHP calcium channel agonist, Bay K 8644, on muscarinic receptors and calcium channels were compared to those of the DHP calcium channel antagonists, nicardipine and nimodipine in the dog cardiac sarcolemma. Bay K 8644, nicardipine and nimodipine inhibited the specific $[^3H]$QNB binding with $K_i$ values of 16.7\mu{M}$, 3.5\mu{M}$ and 15.5\mu{M}$ respectively. Saturation data of $[^3H]$QNB binding with $K_i$ VALUES OF 16.7\mu{M}$ 3.5\mu{M}$ and 15.5\mu{M}$ respectively. Saturation data of $[^3H]$QNB binding in the presence of these DHP drugs showed this inhibition to be competitive. Bay K 8644, like nicardipine and nimodipine, blocked the binding of $[^3H]$nitrendipine to the high affinity DHP binding sites, but atropine did not, indicating that the muscarinic receptors and the DHP binding sites m but atropine did not, indicating that the muscarinic receptors and the DHP bindings sites on calcium channels are distinct. The $K_i$ value of Bay K 8644 for the DHP binding sites was 4nM. Nicardipine and nimodipine $(K_i:0.1-0.2\;nM)$ were at least 20 times more potent than Bay K 8644 in inhibiting $[^3H]$ nitrendipine binding. Thus, the muscarinic receptors were about 4000 times less sensitive than thes high afinity DHP binding sites to Bay K 8644. These results suggest that the DHP calcium agonist Bay K 8644 binds directly to the muscarinic receptors but its interaction with the muscarinic receptors is not related to its binding to the DHP binding sites on calcium channels.

• Journal of Chest Surgery
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• v.41 no.5
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• pp.541-549
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• 2008

Background: Vasoconstrictor-induced reduction in arterial graft diameter can cause significant flow deprivation. The aim of this study was to evaluate the effect of vasodilator pretreatment on vasoconstrictor-induced blood vessel spasm in vitro. Material and Method: Rabbit brachial arteries (BA) and celiac arteries (CA) were cut into rings $(3{\sim}4mm)$ and suspended with a force displacement transducer (TSD $125C^{(R)}$, Biopac Inc. USA) in a tissue bath filled with 5 mL modified Krebs solution bubbled with 5% $CO_2$ and 95% $O_2\;at\;38^{\circ}C$. The rings were contracted with vasoconstrictors, and the developed tension changes were considered control values. The rings were then pre- treated with $30{\mu}M$ nitroglycerin, nicardipine, verapamil, and papaverine, respectively, for 40 minutes and rinsed with the physiologic buffered salt solution three times every 15 min. The vasoconstrictor-induced tension changes after the previous procedure were considered experimental values. Data are expressed as the percentage tension induced by vasoconstrictors before and after pretreatment with vasodilators. Result: Nicardipine depressed vasoconstriction induced by norepinephrine, angiotensin II (All), and U46619 in both the BA and the CA more significantly than did nitroglycerin (p<0.01) and verapamil (p<0.05). Verapamil depressed vasoconstriction induced by 5-hydroxytryptamine (5HT), All, and U46619 in the BA and by 5HT in the CA more significantly than did nitroglycerin (p<0.01). Conclusion: These findings suggest that both nicardipine and verapamil effectively depressed vasoconstrictor action. Nicardipine is thought to be more effective than verapamil for the prevention of vasoconstrictor action.

• Childhood Kidney Diseases
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• v.6 no.2
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• pp.169-177
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• 2002

Purpose: Hypertension accelerates the progression of chronic renal disease, whether it results from, or causes, the renal disease. Therefore, the control of hypertension is one of the important factors that retard the rate of renal deterioration. We compared the effects of different antihypertensive agents on renal function and glomerular morphology In subtotal nephrectomized rats. Materials and methods: After induction of chronic renal failure with 5/6 nephrectomy, the rats were divided into three groups; control group (Group C), enalapril group (Group E), and nicardipine group (Group N). Systolic blood pressure was measured by tail cuff method every 4 weeks until 12 weeks after nephrectomy. At 12 weeks after nephrectomy, all rats were placed in metabolic cages for 24 hour urine collections to measure urinary protein and creatinine excretion. After urine collection and blood sampling for serum creatinine, all rats were sacrificed. The renal tissue was processed for morphometric study with light microscope and electron microscope. Results: 1. The blood pressure of Group C increased progressively, but both enalapril and nicardipine prevented the development of hypertension, and the two drugs were equally effective in maintaining normal blood pressure throughout the study. 2. Twenty-four hour urinary protein excretion was lower in Group E compared to Group C and Group N 3. Mesangial expansion score in both treated groups were significantly lower than the control group. Mean glomerular volume in Group E was significantly reduced compared to Group C and Group N. There was no significant difference in mean glomerular volume between Group C and Group N. 4. There was no significant difference in podocyte structural changes, estimated by filtration slit length density, among control, enalapril and nicardipine treated groups. Conclusion: Control of hypertension with enalapril or nicardipine afforded considerable protection from mesangial expansion in the rat remnant kidney model. But protein excretion and glomerular growth were significantly reduced in Group E compared to Group N. There was no significant difference in podocyte structural changes among the 3 groups.

• The Korean Journal of Pain
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• v.3 no.2
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• pp.144-148
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• 1990

정상인에서 Guanethidine Nicardipine Nitroglycerine Prostaglandin $E_1$을 피하주사하고 지속적인 복사열을 주사한 후에 Pain Meter NYT-5를 이용하여 동통역치를 측정하였다. 통증역치는 Guanethidine과 Nicardipine에 의해 상승되었으며 Nitroglycerine에 의해서는 거의 변화가 없고 Prostaglandin $E_1$에 의해서는 감소되었다. 이러한 변화는 지각신경섬유의 말단 감각수용체에 대한 감수성이 이들 혈관확장제에 대하여 서로 다른 작용을 나타내는것 같다.

• Archives of Pharmacal Research
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• v.13 no.3
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• pp.240-245
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• 1990

Asymmetric 2, 6-dimethyl-4-aryl-1, 4-dihydropyridine-3, 5-dicarboxylate with [N-(3, 4-methylenedioxybenzyl)-N-methyl] aminoethyl group as the ester moiety and related 1, 4-dihydropyridine derivatives were prepared and tested for the effects on vascular smooth muscles. 2-6-dimethyl-4-(3'-nitrophenyl)1-4-dihydropyridine-3, 5-dicarboxylic acid 3-[N-(3', 4-methylenedioxybenzyl-N-methyl] aminoethyl ester 5-methyl ester (11) and 2, 6-dimethyl-4-(3'-nitrophenyl)-1, 4-dihydropyridine-3, 5-icarboxylic acid 3-[N-2', 3'-methylenedioxybenzyl)-N-methyl] aminoethyl ester 5-ethyl ester (150 showed potent vasodilating activities $IC_{50}$($10_{-8}M$) was 2, 6 and 2.7 for 11 and 15, compared with 3.5 for nicardipine.

• Korean Journal of Clinical Pharmacy
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• v.22 no.1
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• pp.1-8
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• 2012

항혈소판제인 티크로피딘과 항고혈압제인 니칼디핀과의 약동학적 상호작용 연구를 위하여 티크로피딘 (3 또는 10 mg/kg)과 니칼디핀의 경구 (4 mg/kg) 및 정맥 (12 mg/kg) 투여하여 본 연구를 시행하였다. 연구방법: 티크로피딘이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다. 결 과: 티크로피딘과 니칼디핀의 병용투여 시 티크로피딘이 니칼디핀의 약물동태 파라미터에 미치는 결과는 다음과 같다. 티크로피딘은 CYP3A4 효소의 활성을 저해 하였으나 P-gp활성에는 영향을 미치지 못하였다. 니칼디핀의 혈중농도곡선하면적 (AUC)는 대조군에 비해 티크로피딘 10 mg/kg 병용투여군에서 유의성 (p < 0.05)있게 증가되었다. 상대적 생체이용률 (RB)은 티크로피딘 병용투여군에서 115-143%로 증가하였다. 결 론: 본 논문에서 흰쥐에 티크로피딘과 니칼디핀을 병용경구투여 시 니칼디핀의 생체이용률 (bioavailability)이 유의성 (p < 0.05)있게 증가된 것은 티크로피딘이 대사효소인 CYP3A4를 억제하여 소장과 간장에서 초회통과효과 (first-pass metabolism)를 감소 시켰기 때문인 것으로 사료된다. 본 실험결과를 토대로 인체에서 티크로피딘과 니칼디핀의 상호작용을 검토한 후 투여용량을 조절하는 것이 바람직하다고 사료된다.

• Journal of Pharmaceutical Investigation
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• v.22 no.2
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• pp.133-137
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• 1992

A novel oral controlled release tablet which may offer more uniform drug level in the body than simple zero-order was developed. The tablet is composed of three layers; outer film layer, middle part compression-coated hydroxypropylmethylcellulose (HPMC) matrix layer, and inner core layer. Each layer contains nicardipine HCl as a model drug. In vitro dissolution test showed that the tablet released the drug in clear three steps; a rapid initial release, followed by a constant rate of release, and then a second phase of fast release of drug. The dissolution characteristics could be modified easily by changing the grade of HPMC, thickness of matrix layer, content of methylcellulose in matrix layer, content of active ingredient in each layer. The pH of dissolution medium did not affect the release profile. This three-step release system is expected to raise the blood concentration rapidly to effective level and to maintain effective blood level longer than simple slow-release systems.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.195-195
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• 1994

병원별 총 추적기간은 602-4,137 인년 이었으며, 병원별 대상자 1인당 추적일수의 중앙값은 34.5-61일 이었다. 병원별 추적 완료율도 35.3-92.3%로 다양하게 나타났다. 대상자중 칼슘차단제의 혈관확장효과에 따른 부작용들의 8주간 누적 발생율을 보면, 안면홍조 23.3%, 두통 13.5%, 심계항진 13.3%, 어지러움 7.6%, 하지부종 6.6% 였다. 그 외 부작용으로는 변비 13예, 소화장애 8예, 오심 6예, 치은비대, 안면부종, 피로감이 각각 2예, 탈모증, 불면증, 허약감, 피부질환, 호흡곤란, 손발저림, 발한, 구강건조 등이 각각 1예 있었다. 안면홍조의 발생율이 남자(12.9%)보다 여자(29.9%)에서 높았으며, 투여한 약제에 따라서 Nitrendipine 34.0%, Nifedipine 26,6%, Nicardipine 17.8%, Amlodipine 12.2%로써 약제별로 차이가 있었다. 두통의 발생율은 40세 미만 32.8%, 40-54세 15,8%, 55세 이상 10.5%로써 연령이 증가할수록 발생율이 낮았다. 하지부종의 발생율도 남자(3.4%)보다 여자(8.6%)에서 높았으며, 투여한 약제에 따라서 Nitrendipine 15.2%, Nifedipine 10.0%, Amlodipine 2, 1%, Nicardipine 0%로써 약제별로 차이가 있었다. 안면홍조가 발생한 환자에서 약물을 계속 투여시 2주후에 63.5%, 4주후에 77.0% 6주후에 88.5%가 소실하여 최초 안면홍조가 발생한 환자중 11.5%에서만 증상이 남아있었다. 약물투여를 중단하게 된 사유는 안면홍조와 두통이 각각 15예, 심계항진 4예, 어지러움 2예, 변비 및 안면부종이 각각 1예로 나타났다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.45-45
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• 1992

Calcium channel에 작용하는 dihydropyridine(DHP) 계열의 calcium channel 효능제와 길항제의 caicium channel에 대한 작용과 muscarinic receptor에 대한 작용과의 관계를 조사하기 위하여 [$^3$H]QNB와 [$^3$H]nitrendipine 결합실험을 시행하고 이를 지표로 하여 칼슘효능제와 길항제의 이들 receptors에 대한 결합성질을 검토하였다. 본 연구결과 칼슘 channel 효능제인 Bay K 8644는 칼슘길항제인 nicardipine 및 nimodipine과 같이 고농도에서 muscarinic receptor에 대한 [$^3$H]QNB결합을 경쟁적으로 억제하였으며 이들 약물의 muscarinic receptor에 대한 Ki치는 각각 16.7 $\mu$M, 3.5 $\mu$M, 및 15.5 $\mu$M이었다. 한편, 이들 약물은 다같이 칼슘 channel의 high affinity DHP결합부위에 대한 [$^3$H]nitrendipine 결합을 억제하였으나 이 부위에 대한 Bay K 8644, nicardipine, 및 nimodipine의 Ki치는 각각 4 nM, 0.1 nM, 및 0.2 nM로서 muscarinic receptor에 대한 Ki치 보다 4,000-75,000배 작았다. 뿐만 아니라 [$^3$H]QNB결합을 완전히 차단하는 고농도의 atropine(1 $\mu$M)에 의해서도 [$^3$H]nitrendipine결합이 전혀 영향을 받지 않았다. 따라서 DHP계 약물의 muscarinic receptor에 대한 작용은 칼슘channel에 대한 이들 약물의 작용을 연구하거나 임상적 치료 목적으로 사용할때는 나타나지 않을 것으로 생각된다.