• The Korean Journal of Physiology and Pharmacology
• /
• v.19 no.5
• /
• pp.413-420
• /
• 2015

Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing ${\alpha}2$ adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce $Ca^{2+}$ release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger $Ca^{2+}$ peak or increase in the presence or absence of external $Ca^{2+}$. When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced $[Ca^{2+}]_i$ signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

• Korean Journal of Biological Psychiatry
• /
• v.2 no.2
• /
• pp.205-217
• /
• 1995

In comparison with tricyclic antidepressants(TCAs), one of the most interesting characteristics of selective serotonin reuptake inhibitors(SSRIs) is its structural differences, reveals different pharmacological properties. The applications at the moment are most effective in clinical applications to depression. The limited result of the research to date on the various applications of SSRIs has not revealed the total potential and applicability of SSRIs. Therefore, attending physicians utilizing SSRIs do not know the full capabilities of the drug on patients and what the patients may reap in terms of benefit from its curing elements. Physicians must first try to understand the full potential of SSRIs and its potential applications for it to be effective on patients. recently, it has been determined that SSRIs and other drugs when administered together may be more effective in the healing process because SSRIs complements and aids in the enhancement and effect of the other drugs. This article is written to give attention to the reader of the pharmacological properties and the clinical use of SSRIs. It is the authors's hope that continuous research on the particular aspects of SSRIs can aid the clinicians in the use of this SSRIs.

• The Korean Journal of Physiology
• /
• v.25 no.2
• /
• pp.147-158
• /
• 1991

The effects of noradrenaline on the spontaneous contraction recorded from a strip of mucosa-free antral circular muscle were studied in the guinea-pig stomach, and the changes in slow waves and membrane resistance were analyzed in order to elucidate the mechanism for the excitatory response to noradrenaline. Electrical responses of circular muscle cells were recorded using glass microelectrodes filled with 3 M KCI. Electrotonic potentials were produced to estimate membrane resistance by the partition stimulating method. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) The spontaneous contractions were potentiated dose-dependently by the application of noradrenaline. 2) Through the experiments using adrenoceptor-blockers, the strong excitatory effect via $[\alpha}-adrenoceptors$ and the weak inhibitory efffect via ${\beta}-adrenoceptors$ were noted. 3) Noradrenaline produced hyperpolarization of membrane potential, and increases in the amplitude and the maximum rate of rise of slow waves. 4) In the presence of apamin, Ca-dependent K channel blocker, the characteristic hyperpolarization was not developed. However, the excitatory effect of noradrenaline on spontaneous contraction remained. 5) Membrane resistance was reduced during the hyperpolarized state by the application of noradrenaline, and the change of membrane resistance and the hyperpolarized state were completely abolished by apamin. From the above results, following conclusions could be made: Excitatory responses to noradrenaline result from the dominant ${\alpha}-excitatory$, and the weak ${\beta}-inhibitory$ action of noradrenaline. Hyperpolarization of membrane potential by noradrenaline is due to the activation of Ca-dependent K channel.

• Journal of Acupuncture Research
• /
• v.20 no.4
• /
• pp.11-23
• /
• 2003

Objective: In this study, the analgesic effect of gold injection aqua-acupuncture on CFA induced arthritis in rats was inverstigated. Furthermore, to determine the antinociceptive mechanism of gold injection aqua-acupuncture, naloxone and yohimbine were administrated intraperitoneally 15min prior to the gold injection aqua-acupuncture. Methods: The experimental groups were divided into 6 groups. Control group, NSI, AMI, AMI+SL : AMI+Nx, AMI+Yb. Thereafter we measured the chages of TFL between control and experimental groups. Results: 1. The tail flick latency induced by CFA was significantly increased on AMI as compared with the NSI group. 2. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of naloxone. The anti-nociceptive effect of AMI was completely antagonized by naloxone(an opioid receptor antagonist). 3. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of yohimbine. The anti-nociceptive effect of AMI was completely antagonized by yohimbine(${\alpha}2$-adrenoceptor antagonist). Conclusions: According to the results, gold injection aqua-acupuncture has significant analgesic effects on adjuvant induced arthritis in rats and the effect of anti-nociception was mediated by opiodergic system and ${\alpha}2$-adrenergic system.

• 전기의세계
• /
• v.41 no.12
• /
• pp.21-30
• /
• 1992

내연기관의 가솔린자동차보다 역사가 오래된 전기자동차는 상대적으로 주생성능과 가격 경쟁력의 열세로 그 자취를 감추었고 최근까지 주로 특수목적의 단거리 저속차량으로 사용되고 있다. 그러나 1890년대 후반부터 전세계가 자동차배기가스에 의한 대기오염과 지구온난화 현상등의 문제를 심각하게 공감하게 되었고 마침내 미국 캘리포니아주에서는 전가자동차의 강제판매를 규정화하게 이르렀다. 이 규정에 의하면 1998년도부터 차량 판매대수의 2%를 전기자동차 판매로 강제요구하고 있다. 이 비율은 2000녀도에 5% 2003년에는 10%로 늘어날 계획이다. 따라서 미국에 많은 자동차를 수출하고 있는 일본, 독일 및 여러 유럽국가에서는 이 사업에 막대한 자금을 투자하며 개발에 몰두하고 있다. 미국의 Big3도 에너지성의 도움으로 최근 USABC를 결성하여 전기자동차 개발에 박차를 가하고 있다. 지금까지 기존의 가솔린자동차 기술에 있어서 일본과 독일에 상대적 열세에 있었던 미국도 이번 캘리포니아주의 전기자동차 강제판매 규정에 따른 전기자동차 사업으로 미국자동차 시장의 새로운 판도를 조성하겠다는 의도인듯하다. 국내에서도 정부가 이 사업의 중요성을 심각히 인식하고 G7사업과제의 하나로 선정하여 산, 학, 연 각층의 전문가가 참여하여 성공적으로 개발을 마칠 수 있도록 적극 지원하고 있다. 지금까지의 평균주행성능을 보면 최고속도 100-120km/h, 일층전 최대주행거리 150-200km 정도이며, 아직 양산체제에 돌입하지 않았기 때문에 가격면에서 경쟁력이 없는 실정이다. 그러나 1990년도에 들면서 각종 요소부품들의 기술수준이 급성장을 이루어서 앞으로 10년정도 후면 성능과 가격면에서 가솔린자동차와 대등한 수준의 전기자동차 개발이 실현될 수 있으리라 예측된다.는 영향받지 않았다. Clonidine의 심박수 감소작용은 .뇌실내및 정맥내 diltiazem이나 nifedipine 처리후에 감약되었다. 5). 뇌실내 clonidine$(30{\mu}g)$ 처 리후 뇌실내 diltiazem$(400{\mu}g)$과 nifedipine$(350{\mu}g)$의 혈압하강및 심박수 감소효과는 영향 받지 않고 그대로 나타났다. 이상의 결과로 diltiazem과 nifedipine은 가토뇌내에서 methoxamine에 의한 혈압상승의 작용점인 alrfia-1 adrenoceptor의 흥분에는 영향을 미치지 못하나 clonidine의 작용점인 alpha-2 adrenoceptor의 흥분에 의한 혈압하강및 심박수 감소효과는 억제한다고 추론하였다.thin 함량은 110.6 mg/L로서 산업적인 생산성이 있는 것으로 나타났다. 이번 연구를 통하여 개발된 변이주 B76 및 이의 대량 발효를 위한 최종조건의 정립은 향후 astaxanthin의 산업적 생산공정에 필요한 기초자료로 이용될 것으로 기대된다.색총말내에 소형의 도형, 소형의 장형 연접소포 및 DENSE CORE VESICLE의 3가지 연접소포를 가지고 있었고 출현빈도수는 촉각엽에서 가장 큰 33%이었다. 제5형 신경연접은 축색종말내에 중등도크기의 원형, 대형의 원형연접소포 및 DENSE CORE VESICLE을 포함하였고 13%의 출현빈도수로 관찰되었다. 배추횐나비의 촉각에 있는 지각신경세포가 뇌의 촉각엽으로 뻗어 들어가 위의 5가지 신경연접중 어느 형을 형성하는지를 관찰하기 위하여 좌측 촉각의 기부를 제거하여 지각신경세포를 절단하였는데 그 결과, 좌측 촉각엽에서 제4형의 신경연접이 퇴행성 변화를 나타내었다.

• Korean Journal of Acupuncture
• /
• v.30 no.4
• /
• pp.220-229
• /
• 2013

Objectives : Electroacupuncture(EA) has been used effectively in producing analgesia on ankle sprain pain of humans and animals. Currently to examine the underlying mechanisms of the EA-induced analgesia, the effects of EA on weight-bearing forces(WBR) were examined at ankle sprain classified as grade 3 in rats. Methods : The severe ankle sprain classified as grade 3 was induced surgically by ankle ligament injury in the Sprague-Dawley rats. WBR of the affected foot were examined to evaluate effects and mechanism of EA(2 Hz, 1 ms pulse width, 2 mA intensity, for 15 min) which was applied to either SI6, GB34, or GB39 acupoints. The rats were pretreated with naltrexone(10 mg/kg, i.p.) as an opioid receptor antagonist or phentolamine(5 mg/kg, i.p) as an ${\alpha}$-adrenoceptor antagonist at 30 min before EA. Results : The daily repeat EA at either SI6, GB34, or GB39 showed significant analgesic effects on the severe ankle sprain. Particularly, daily EA at GB34 showed more potent analgesic effect than the others. In addition, the naltrexone pretreatment completely blocked the analgesic effect of EA at GB34, indicating the involvement of the endogenous opioid system in mediating the effect of EA at GB34. However, the phentolamine pretreament blocked analgesic effects of EA at either SI6 or GB39, indicating the involvement of ${\alpha}$-adrenoceptors in mediating the effect of EA at either SI6 or GB39. Conclusions : These data suggest that EA-induced analgesia on ankle sprain pain is mediated through either endogenous opioids or ${\alpha}$-adrenoceptors dependant on acupoint specific pattern.

• Biomolecules & Therapeutics
• /
• v.1 no.1
• /
• pp.1-8
• /
• 1993

It has been known that calcium antagonists also inhibit the radioligand binding to muscarinic and $\alpha$-adrenergic receptors and, in case of verapamil, these inhibitions may play a role in the effects of verapamil on the heart. In this study, the effects of nicardipine, nifedipine, nimodipine, diltiazem and verapamil on the binding of [$^3H$]dihydroalprenolol (DHA) to dog cardiac ${\beta}$-adrenergic receptors were examined. A single uniform [$^3H$]DHA binding site ($K_D/= 5nM\;and\;B_{max}=2600$ fmol/mg protein) was identified in dog cardiac sarcolemma. [$^3H$]DHA binding was not affected by the usual therapeutic concentrations of these calcium antagonists (nanomolar range) but in the "nonspecific"concentration ranges ($28-180{\mu}m$) these drugs inhibited [$^3H$]DHA binding to $\beta$-adrenergic receptors. Nicardipine, nifedipine, nimodipine and diltiazem competed for [$^3H$]DHA binding to ${\beta}$-adrenergic receptors with dissociation constants ($K_i$) of $28{\mu}m,\' 74{\mu}m, 39{\mu}m \;and \;35{\mu}m,$ respectively. Verapamil ($K_i=176.5 {\mu}m$) was less potent inhibitor than other drugs and this inhibition was noncompetitive; the maximal binding capacity ($B_{max}$) $300 {\mu}m$ verapamil without change in the apparent dissociation constant (4K_D$) for DHA. These results indicate that the inhibitory action of calcium antagonists at high concentrations on ${\beta}$-adrenergic receptors is not involved in the therapeutic effects of these drugs by the calcium channel blocking action.

• YAKHAK HOEJI
• /
• v.41 no.6
• /
• pp.797-801
• /
• 1997

Recently we reported that water extracts of Coptidis Rhizomas showed calcium antagonistic action and alpha-adrenoceptor inhibitory action in the vascular smooth muscle. Since ca lcium antagonistic properties are important in the treatment of various diseases including asthma. In the present study, the bronchodilatory effects of crude extract of three kinds of Coptidis Rhizoma (Coptidis chinensis, Coptis japonica and root hair of Coptis japonica) was investigated using rat isolated trachea. The result showed that all extracts relaxed carbachol-contracted tracheal smooth muscle. Concentration-dependently, in which the root hair of Coptis japonica was the least potent. The inhibitory potency expressed in terms of $IC_{50}$ against carbachol contraction was 1.8${\mu}$g/ml and 2.7${\mu}$g/ml for Coptidis chinensis and Coptis japonica, respectively. These extracts also inhibited KCI-contracted tracheal smooth muscle. But the relative potency ($IC_{50}$) was 3.5 and 4.1 folds weaker than carbachol-induced contraction for Coptidics chinenesis and Coptis japonica, respectively. Pretreatment of crude extracts also inhibited carbachol- or KCI-induced contraction, non-competitively. These findings indicate that the extracts have muscarinic blocking as well as $Ca^{2+}$ channel blocking action. When provoked intracellular stored $Ca^{2+}$ release by carbachol in $Ca^{2+}$-free conditions, initial phasic contraction due to $Ca^{2+}$ release was significantly inhibited by the extracts. As taken together, we conclude that water extracts of Coptidis Rhizoma may be beneficial in bronchospasm or other broncheal tube narrowing conditions such as asthma.

• Journal of Pharmaceutical Investigation
• /
• v.30 no.1
• /
• pp.61-65
• /
• 2000

Doxazosin, a postsynaptic selective ${\alpha}1-adrenoceptor$ antagonist, is a potent antihypertensive agent which reduces peripheral resistance and blood pressure by vasodilatation of peripheral vessels. It is also used in the treatment of urinary obstruction by benign prostatic hypertrophy. The purpose of the present study was to evaluate the bioequivalence of two doxazosin tablets, $Cardura^{TM}$ (Pfizer Korea Ltd.) and $Cardil^{TM};$ (Kyungdong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen normal male volunteers, $24.19{\pm}2.48$ years in age and $62.41{\pm}6.66$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of doxazosin was orally administered, blood was taken at predetermined time intervals and the concentrations of doxazosin in serum were determined with an HPLC method using spectrofluorometric detector. Pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets were -1.54%, -1.51 % and 3.42%, respectively, when calculated against the $Cardura^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t,\;C_{max}\;and\;T_{max}$ were all more than 99.00%. Minimum detectable differences $(\Delta)$ at ${\alpha}=0.05\;and\;1-{\beta}=0.8$ were all less than 20% (e.g., 12.73%, 12.84% and 13.01% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The 90% confidence intervals were all within :${\pm}20%$ (e.g., $-8.97{\sim}5.90,\;-9.01{\sim}6.00\;and\;-4.16{\sim}11.05\;for\;AUC_t,\;C_{max}\;and\;T_{max},\;respectively)$. All of the above para- meters met the criteria of KFDA for bioequivalence, indicating that $Cardil^{TM}$ tablet is bioequivalent to $Cardura^{TM}$ tablet.

• The Korean Journal of Pharmacology
• /
• v.25 no.1
• /
• pp.13-21
• /
• 1989

The circadian rhythm of spontaneous motor activity was not significantly altered by $T_4$(4mg/kg, i.p. inj. once a day for 5 days: $T_4$) and PTU (fed ad lib in 0.01% drinking water for 5 weeks: PTU). The plasma thyroxine level was markedly increased by $T_4$ but reduced by PTU, and the plasma thyrotropin level was markedly increased by PTU but moderately increased by $T_4$. Clonidine slightly increased the plasma CS level, but the clonidine effect was significantly enhanced by $T_4-pretreatment$. The brain NE and MHPG contents were little affected by $T_4$ but the NE content was significantly decreased by PTU. The SS-induced increase of plasma CS level was moderately decreased by PTU but increased by $T_4$. However, clonidine significantly inhibited the SS-induced increase, and the inhibitory effect of clonidine was not significantly affected by PTU and $T_4$, respectively. The brain MHPG content and MHPG/NE ratio were significantly decreased by clonidine but increased by SS. The clonidine- and SS-induced changes of brain MHPG content and MHPG/NE ratio were not altered by $T_4$. PTU did not affect the SS-induced increase of brain NE turnover but significantly attenuated the clonidine-induced decrease. The SS-induced increases of brain MHPG content and MHPG/NE rtatio were markedly inhibited by clonidine, and the inhibitory effect of clonidine was not affected by $T_4$ and PTU, respectively. These results suggest that the responses to swim-stress is not signigicantly affected by the alteration of thyroid function and that the hypothalamo-adenohypophysis-adrenocortical stimulation in response to swim-stress seems to be mediated via hypothalamic noradrenergic activation, and the stress response may be inhibited by the agonistic activity of clonidine on the presynaptic ${\alpha}_2-adrenoceptor$.