• Journal of Dental Anesthesia and Pain Medicine
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• 제21권5호
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• pp.379-396
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• 2021

Background: Trigeminal neuralgia (TN) is characterized by brief, unilateral, sharp, stabbing, and shooting pain of the fifth cranial nerve. The objective of this systematic review with meta-analysis was to determine the effect of medications compared to placebo in adult patients with TN. Methods: Review authors identified randomized placebo-controlled trials (RCTs) from PubMed, Web of Science, Cochrane, and EMBASE up to February 2021. We assessed the inclusion and exclusion criteria as well as the risk of bias of the studies based on the Cochrane Handbook. A total of 324 unduplicated references were scanned independently and reduced to eight relevant RCTs, with 89 patients included. Medications investigated included oral carbamazepine, subcutaneous sumatriptan, lidocaine (intranasal, 8% spray on the oral mucosa or intravenous), buprenorphine (ganglionic local opioid analgesia), and oral Nav1.7, a selective sodium channel blocker. Results: Meta-analyses showed that overall patients receiving lidocaine reported a significantly lower post-treatment intensity of pain -3.8 points on a 0-10 scale (95% Cl = -4.653 to -2.873; P < 0.001). Patients who received lidocaine were 8.62 times more likely to have pain improvement than patients on placebo (P < 0.001). In one RCT, patients receiving oral carbamazepine showed a significant improvement in pain intensity of -32% compared to the placebo (P < 0.001). In one trial, patients receiving 3 mg subcutaneous sumatriptan had a significantly lower intensity of pain on average -6.1 points on a scale of 0-10 compared to placebo (P < 0.001) and a significant improvement in pain intensity of -75% compared to the improvement in the placebo group (P < 0.001). Patients who received subcutaneous sumatriptan were 10 times more likely to have pain improvement than those who received placebo (P = 0.001) in one study. Due to the unclear/high risk of bias and small sample size, the quality of the evidence for lidocaine in the treatment of TN was low. Conclusion: Further studies are needed for carbamazepine, sumatriptan, buprenorphine, and oral Nav1.7 sodium channel blockers, as only one study reported outcomes.

• 대한본초학회지
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• 제26권4호
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• pp.75-81
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• 2011

Objectives : Magnoliae officinalis Cortex (MOC) has been used in traditional medicine for digestive diseases in Korea, China and Japan. However, Machili thunbergii Cortex (MTC) also has been used as a substitute of MOC in Korea sometimes. Thus, this study was carried out to investigate and compare the effects of MOC and MTC on intestinal motility of isolated small intestinal segments from ICR mouse. Methods : Changes in motility were recorded via isometric transducers connected to a data acquisition system and amplitude, frequency and area under the curve (AUC) of intestinal spontaneous phasic contraction were compared. Results : The MOC extracts ($1{\sim}{\mu}g/mL$) dose-dependently decreased both amplitudes and frequencies of the spontaneous phasic contraction, but not AUC. However, high concentration of MOC (100 ${\mu}g$/mL) evoked tonic contraction. And it was not inhibited by tetrodotoxin, a sodium channel blocker, and nifedipine, a L-type $Ca^{2+}$ channel antagonist. These results suggested that MOC (100 ${\mu}g$/mL)-induced tonic contraction is not mediated by nerve or L-type $Ca^{2+}$ channel. On the other hand, the MTC extracts dose-dependently inhibited amplitude and AUC, but not the frequency. Conclusions : Although both MOC and MTC affected intestinal motility, MOC is more effective on intestinal motility than MTC. And MOC has been used as a traditional medicine for a long time but not MTC. Thus, we suggested that MTC should not be used in Korea as a substitute of MOC and MOC might be useful traditional medicine for gastrointestinal disease. The mechanism of MOC is still remained to elucidate.

• The Korean Journal of Physiology
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• 제20권1호
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• pp.17-29
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• 1986

갑상선 호르몬의 표적기관(target organ) 중의 하나인 심장이 hyperthyroid상태에서 심박동수의 증가, 부정맥 그리고 세포 수들에서 sodium, potassium pump기능이 항진되는 것으로 보고되고 있다. 증진된 Pump기능과 더불어 positive chronotropic effect는 심장의 향도잡이로 알려진 동방결절 과 심방근에 어떤 변화에 의하여 발현되는지 알아보기 위하여 $3{\sim}6$개월령의 토끼 (체중 약 1.5kg내외)에 3,3',5-l-triiodothyronine$(T_3)$을 투여하며 실험적으로 hyperthyroid상태를 유도한 다음 심장세포 내에 유리미세전극을 삽입하여 기록한 결과 다음과 같은 성적을 얻었다. 1) 심박동수는 투여 전(Day 1) $169.0{\pm}28.0\;beat/min(Day\;7)$에서 $264.2{\pm}18.9\;beat/min(Day\;7)$으로 156% 가량 증가되었고 체중은 투여전 체중의 $68.2{\pm}2.0%$로 현저한 감소를 보였다. 2) $T_3$투여군에서 활동전압기간은 $148.0{\pm}29.1\;msec$에서 $107.0{\pm}13.6\;msec$로 감소하여 심박동증가를 반영하였으나 그 외의 활동전압 Parameter에서 대조군과 유의한 차를 관찰할 수 없었다. 3) 세포막에 대한 Potassium ion투과성의 영향을 알아보기 위하여 10, 15, $20mM-K^+\;Tyrode$용액을 사용한 결과 SA node에서 $15mM\;K^+$에서 활동전압 발사가 대조군에 비해 현저하게 감소하였고, 4) Ta 투여군에서 심방근의 안정막전압 탈분극 정도는 15mM(P<0.05), $20mM-K^+Tyrode$용액(P<0.05)에서 대조군보다 유의성있게 낮았다. 5) Sodium, potassium pump기능은 대조군에 비해 동방결절$(13.4{\pm}1.1\;vs.\;19.5{\pm}7.1mV,\;p<0.1)$과 심방근$(15.1{\pm}5.5\;vs.\;25.8{\pm}10.0mV,\;p<0.025)$에서 모두 높은 값을 얻었다. 6) $T_3$에 의한 calcium ion의 영향을 알아보기 위하여 $Ca^{++}\;channel\;blocker$로 $MnCl_2$를 사용한 결과 $T_3$ 투여군의 동방결절은 정상대조군의 것보다 낮은 농도의 $MnCl_2$ 용액에서 흥분성의 감소를 보였다.

• 대한한방내과학회지
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• 제21권3호
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• pp.377-388
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• 2000

Objective : This study was undertaken to evaluate the effect of Sunghyangchungisan (SHCS) on the regulation of vascular tone and $Ca^{2+}$ metabolism in arterial tissues. Vascular rings isolated from rabbit carotid artery were myographed isometrically in isolated organ baths and the effect of SHCS on contractile activities, endothelial function and $Ca^{2+}$ metabolism were determined. Methods : In phentobarbital sodium-anesthetized rabbits, SHCS administered through ear vein (100 mg/Kg body wt.) or intragastric dwelling tube (300 mg/Kg body wt.) attenuated phenylephrine (PE, 10 ${\mu}g$/Kg, i.v.)-induced increases in both systolic and diastolic cartoid arterial blood pressure. Results : In experiments with isolated arterial strips, SHCS relaxed arterial rings which were pre-contracted by phenylephrine (PE, 1 ${\mu}M$). The responses to SHCS were partially dose-dependent at concentrations lower than 0.5 mg/ml. When SHCS was applied prior to the exposure to PE, it inhibited the PE-induced contraction by a similar magnitude which was comparable to the relaxation of pre-contracted arterial rings. Washout of SHCS after observing its relaxant effect resulted in a full recovery of PE-induced contractions, indicating that the action mechanism is reversible. The observation that SHCS did not change the $ED_{50)$ of PE oh its dose-response curve ruled out the possible interaction of SHCS with ${\alpha}$-receptors. The relaxant effect of SHCS was not affected by removal of endothelium or a nitric oxide synthase inhibitor, L-NAME. Methylene blue, an inhibitor of the soluble guanylate cyclase, did not affect the relaxant effect of SHCS. These results suggest that the action of SHCS is not mediated by the endothelium nor soluble guanylate cyclase. Constant cGMP production determined in arterial strips in the presence or absence of SHCS is consistent with this conclusion. When contraction was induced by additive application of $Ca^{2+}$ in arterial rings which were pre-depolarized by high $K^+$ in a $Ca^{2+}$-free solution, the relaxant effect of SHCS was attenuated by increasing the $Ca^{2+}$ concentration. SHCS, when applied to the arterial rings pre-contracted by PE and then relaxed by nifedipine, a $Ca^{2+}$ channel blocker, did not show additive relaxation. SHCS partially blocked $Ca^{2+}$ influx stimulated by PE and high $K^+$ which was determined by 5-min ^{45}Ca$ uptake, while it did not affect $Ca^{2+}$ efflux. Conclusions : From above results, it is suggested that SHCS relax PE-induced contraction of rabbit carotid artery in an endothelium independent manner, andinhibition of $Ca^{2+}$ influx may contribute to the underling mechanism.

• The Korean Journal of Physiology and Pharmacology
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• 제20권6호
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• pp.629-639
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• 2016

The present study was designed to investigate the characteristics of gintonin, one of components isolated from Korean Ginseng on secretion of catecholamines (CA) from the isolated perfused model of rat adrenal gland and to clarify its mechanism of action. Gintonin (1 to $30{\mu}g/ml$), perfused into an adrenal vein, markedly increased the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. The gintonin-evoked CA secretion was greatly inhibited in the presence of chlorisondamine ($1{\mu}M$, an autonomic ganglionic bloker), pirenzepine ($2{\mu}M$, a muscarinic $M_1$ receptor antagonist), Ki14625 ($10{\mu}M$, an $LPA_{1/3}$ receptor antagonist), amiloride (1 mM, an inhibitor of $Na^+/Ca^{2+}$ exchanger), a nicardipine ($1{\mu}M$, a voltage-dependent $Ca^{2+}$ channel blocker), TMB-8 ($1{\mu}M$, an intracellular $Ca^{2+}$ antagonist), and perfusion of $Ca^{2+}$-free Krebs solution with 5mM EGTA (a $Ca^{2+}$chelater), while was not affected by sodium nitroprusside ($100{\mu}M$, a nitrosovasodialtor). Interestingly, LPA ($0.3{\sim}3{\mu}M$, an LPA receptor agonist) also dose-dependently enhanced the CA secretion from the adrenal medulla, but this facilitatory effect of LPA was greatly inhibited in the presence of Ki 14625 ($10{\mu}M$). Moreover, acetylcholine (AC)-evoked CA secretion was greatly potentiated during the perfusion of gintonin ($3{\mu}g/ml$). Taken together, these results demonstrate the first evidence that gintonin increases the CA secretion from the perfused rat adrenal medulla in a dose-dependent fashion. This facilitatory effect of gintonin seems to be associated with activation of LPA- and cholinergic-receptors, which are relevant to the cytoplasmic $Ca^{2+}$ increase by stimulation of the $Ca^{2+}$ influx as well as by the inhibition of $Ca^{2+}$ uptake into the cytoplasmic $Ca^{2+}$ stores, without the increased nitric oxide (NO). Based on these results, it is thought that gintonin, one of ginseng components, can elevate the CA secretion from adrenal medulla by regulating the $Ca^{2+}$ mobilization for exocytosis, suggesting facilitation of cardiovascular system. Also, these findings show that gintonin might be at least one of ginseng-induced hypertensive components.

• Journal of Yeungnam Medical Science
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• 제8권2호
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• pp.95-105
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• 1991

흰쥐 적출소장의 수축성에 미치는 GABA의 영향을 관찰하여 다음과 같은 결과를 얻었다. 1. GABA는 소장을 이완시켰으며 그 이완 작용은 십이지장, 공장 그리고 회장의 순이었다. GABA A수용체 효현제인 muscimol 역시 소장을 이완시켰으며, 그 효능의 강도는 십이지장, 공장 그리고 회장의 순이었다. 그러나 GABA B수용체 효현제인 baclofen은 소장의 운동성에 유의한 영향을 미치지 못하였다. 2. 상경적 GABA A수용체 길항제인 bicuculline과 비 상경적 GABA A수용체 길항제인 picrotoxin은 십이지장에 대한 GABA와 muscimol의 이완 작용을 현저히 억제시켰다. 그리고 bicuculline의 억제 작용이 picrotoxin 보다 강하였다. 3. Sodium channel blocker인 tetrodotoxin은 GABA의 이완 작용을 봉쇄하였다. 4. 신경절 봉쇄적인 hexamethonium은 십이지장에 대한 GABA의 이완작용을 길항하지 못하였다. 이상의 실험 결과로 볼 때 흰쥐 소장의 자발 수축운동에 대한 GABA의 이완작용은 소장이 부위에 따라 다르게 나타나며, 그 작용은 postganglionic presynaptic neuron에 존재하는 GABA A 수용체에 작용함으로써 나타나는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.9-14
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• 2016

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

• Journal of Pharmaceutical Investigation
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• 제26권1호
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• pp.33-41
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• 1996

In order to study the effect of phenobarbital(PB) on the hepatic transport of diltiazem(DTZ), $Ca^{2+}$ channel blocker, we used isolated hepatocytes of rat which was intraperitoneally pretreated with phenobarbital sodium(75 mg/kg) for four days once a day. For the isolation of rat liver cells, a modification of the two step procedure of Seglen was used. DTZ was dissolved in incubation buffer to the final DTZ concentrations of 200, 400, 600, 800 and 1000 ng/ml in order to elucidate the uptake characteristics of DTZ by hepatocytes. Reactions were stopped at 10, 20, 30, 45, 60, 90, 120 and 300 sec. The initial velocity was determined by disappearance of diltiazem in the hepatocyte suspension. On the other hand, to determine the effect of PB on the in vitro hepatic intrinsic clearance of DTZ we obtained the metabolism rates of DTZ in the control and the PB-pretreated rat hepatocyte at various time intervals. According to pretreatment with PB, the size of hepatocyte and the amount of protein per $10^6$ cells were significantly (p<0.01) increased from $26.92{\pm}0.1364\;m$ to $35.31{\pm}1.00\;m$ and from $468{\pm}6.5\;{\mu}g/10^6$ cells to $628.8{\pm}12.1{\mu}g/10^6$ cells, respectively. In the case or hepatic uptake of diltiazem, $K_m$ was not different in the normalization by cell numbers and increased from $2.90\;{\mu}M\;to\;13.89\;{\mu}M$ in the normalization by protein amount. $V_max$ was increased regardless of normalization by protein amount and cell numbers, from $1.21\;{\mu}mole/min \;{\cdot}\;mg\;protein\;to\;3.96\;{\mu}mole/min\;{\cdot}\;mg\;protein\;and\;from\;2.38\;{\mu}mole/min\;{\cdot}\;10^6\;cells\;to\;2.83\;{\mu}mole/min\;{\cdot}\;10^6\;cells$, respectively. The in vitro hepatic intrinsic clearance of DTZ was significantly (p<0.01) increased from $0.640{\pm}0.038\;ml/mim\;{\cdot}\;10^6\;cells\;to\;2.385{\pm}0.212\;ml/min\;{\cdot}\;10^6\;cells$ due to PB-pretreatment. These results suggest that the uptake of DTZ by hepatocyte is extremely fast and PB enhances the hepatic intrinsic metabolic clearance of DTZ.