• Korean Journal of Veterinary Research
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• v.37 no.2
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• pp.331-338
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• 1997

최근 동물의 진통 및 진정을 목적으로 널리 사용되고 있는 imidazole 유도체인 clonidine, medetomidine, etomidate 등의 약물과 xylazine의 효과를 발정정지기의 척출 돼지 자궁근에서 검토하였다. Clonidine($10^{-8}{\sim}10^{-6}M$)이나 medetomidine($10^{-8}{\sim}10^{-6}M$)은 xylazine과 비슷한 정도로 용량의존적인 자궁근의 수축을 일으켰다. Clonidine, medetomidine, xylazine 등의 $EC_{50}$는 각각 24.7nM, 19.9nM, 45.1nM이었다. 그러나 etomidate는 $10^{-6}M$ 미만의 농도에서 반응이 거의 없었으며, $10^{-6}M$ 이상에서 수축반응을 일으켰다. 이들 agonists의 효과는 yohimbine($10^{-8}{\sim}10^{-6}M$), idazoxan($10^{-7}{\sim}10^{-5}M$), tolazoline($10^{-7}{\sim}10^{-5}M$) 등의 ${\alpha}_2-adrenoceptor$ antagonists에 의해서 차단되었으나, ${\alpha}_1-adrenoceptor$ antagonist인 prazosin ($10^{-6}M$)에 의해서는 차단되지 않았다. 또한 $Ca^{2+}-free$ medium이나 verapamil($10^{-5}M$)의 전처치에 의해서 이들 agonist의 효과가 완전히 차단되었다. 결론적으로 발정정지기의 돼지 자궁근에서 clonidine, medetomidine, etomidate, xylazine 등은 ${\alpha}_2-adrenoceptors$의 흥분을 통해 자궁근의 수축을 일으키며, 이 효과는 voltage-dependent $Ca^{2+}$ channels을 통한 extracellular $Ca^{2+}$ influx의 증가에 의한 것으로 추론하였다.

• The Korean Journal of Pain
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• v.27 no.4
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• pp.313-320
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• 2014

Dexmedetomidine, an imidazoline compound, is a highly selective ${\alpha}_2$-adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties. In order to minimize the patients' pain and anxiety during minimally invasive spine surgery (MISS) when compared to conventional surgery under general anesthesia, an adequate conscious sedation (CS) or monitored anesthetic care (MAC) should be provided. Commonly used intravenous sedatives and hypnotics, such as midazolam and propofol, are not suitable for operations in a prone position due to undesired respiratory depression. Dexmedetomidine converges on an endogenous non-rapid eye movement (NREM) sleep-promoting pathway to exert its sedative effects. The great merit of dexmedetomidine for CS or MAC is the ability of the operator to recognize nerve damage during percutaneous endoscopic lumbar discectomy, a representative MISS. However, there are 2 shortcomings for dexmedetomidine in MISS: hypotension/bradycardia and delayed emergence. Its hypotension/bradycardiac effects can be prevented by ketamine intraoperatively. Using atipamezole (an ${\alpha}_2$-adrenoceptor antagonist) might allow doctors to control the rate of recovery from procedural sedation in the future. MAC, with other analgesics such as ketorolac and opioids, creates ideal conditions for MISS. In conclusion, dexmedetomidine provides a favorable surgical condition in patients receiving MISS in a prone position due to its unique properties of conscious sedation followed by unconscious hypnosis with analgesia. However, no respiratory depression occurs based on the dexmedetomidine-related endogenous sleep pathways involves the inhibition of the locus coeruleus in the pons, which facilitates VLPO firing in the anterior hypothalamus.

• YAKHAK HOEJI
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• v.32 no.1
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• pp.55-61
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• 1988

To elucidate one of the effect of piperine on the peripheral sympathetic nervous system, influence of piperine upon the contractile action of norepinephrine, methoxamine and tyramine as well as uptake and release of $[^{3}H]-norepinephrine$ has been investigated in naive and chronic piperine-treated vas deferens of rats. $pA_2$ value for ${\alpha}_1-adrenoceptor$ of phentolamine was significantly increased. Chronic piperine-treated group was markedly shown increased efflux of $[^{3}H]-norepinephrine$ and muscular tension, but was not affected the neuronal up-take and release of $[^{3}H]-norepinephrine$. It can be concluded that potentiation of the effect of norepinephrine by acute and chronic piperine treated group may be due to the change of affinity of ${\alpha}_1-adrenoceptor$, and partly due to possible modification of storage mechanism.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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• pp.461-469
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethy-lamines, and many of them, especially with 6,7-disubstitution, demonstrate relatively high affinity for catecholamines. Two -OH groups at 6 and 7 positions are supposed to be essential to exert ?${\beta}-receptor$ activities. However, it is not clear whether -OH at 6,7 substitution of THIs also shows ?${\alpha}-adrenoceptor$ activities. In the present study, we investigated whether -OH or $-OCH_3$ substitutions of 6,7 position of THIs differently affect the ?1-adrenoceptor affinity. We synthesized two 1-naphthylmethyl THI alkaloids, $1-{\beta}-naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline$ HBr (YS 51) and $1-{\beta}-naphthylmethyl-6, 7-dimethoxy-1,2,3,4-tetrahydroisoquinoline$ HCl (YS 55), and their pharmacological actions on ?${\alpha}_1-adrenoceptor$ were compared. YS 51 and YS 55, concentration-dependently relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.89{\pm}0.21$ and $5.93{\pm}0.19$, respectively. Propranolol (30 nM) did not affect the relaxation-response curves to YS 51 and YS 55. Concentration-response curves to PE were shifted to right by the pretreatment with YS 51 or YS 55. The $pA_2$ values of YS 51 and YS 55 showed $6.05{\pm}0.24$ and $5.88{\pm}0.16$, respectively. Both probes relaxed KCl (65.4 mM)-contracted aorta and inhibited $CaCl_2-induced$ contraction of PE-stimulated endothelium- denuded rat thoracic aorta in $Ca^{2+}-free$ solutions. In isolated guinea pig papillary muscle, 1 and 10 ${\mu}M$ YS 51 increased contractile force about 4- and 8- fold over the control, respectively, along with the concentration-dependent increment of cytosolic $Ca^{2+}$ ions. While, 10 ${\mu}M$ YS 55 reduced the contractile force about 50 % over the control and lowered the cytosolic $Ca^{2+}$ level, in rat brain homogenates, YS 51 and YS 55 displaced $[^3H]prazosin$ binding competitively with Ki 0.15 and 0.12 ${\mu}M$, respectively. However, both probes were ineffective on $[^3H]nitrendipine$ binding. Therefore, it is concluded that two synthetic naphthylmethyl-THI alkaloids have considerable affinity to ?1-adrenenoceptors in rat aorta and brain.

• Journal of Acupuncture Research
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• v.22 no.1
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• pp.99-108
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• 2005

Objective : The aim of this study is to investigate the analgesic effect and its mechanism of bee venom acupuncture on collagen-induced arthritis(CIA) rats. Methods : Bee venom (1 mg/kg) was subcutaneously punctured into Choksamni (ST36) of CIA Analgesic effect was evaluated by using the tail flick latency (TFL). Opioid and ${\alpha}2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist and yohimbine as ${\alpha}2$-adrenoceptor antagonist prior to bee venom cupuncture. Results : The results were as follows; 1. The TFL for the CIA rat was decreased as time went by. 2. The TFL in CIA rat was increased in bee venom acupuncture group compared with control group (no treatment). 3. Analgesic effect of bee venom acupuncture was not abolished by naloxone pre-treatment in the CIA rat. 4. Analgesic effect of bee venom aqua-acupuncture was abolished by yohimbine pre-treatment in the CIA rat. 5. Two weeks bee venom acupuncture had the continous analgesic effect for 4 weeks. Conclusions : Bee venom acupuncture has an analgesic effect on the CIA rat and has an antinociception mediated by ${\alpha}2$-adrenergic system.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.323-330
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats' isolated atria and aorta. In addition, a $[^3H]$ prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have ?${\alpha}$-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.56{\pm}0.32$ and $5.55{\pm}0.21$, $5.99{\pm}1.16$ and $5.57{\pm}0.34$, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right and resulted in $pA_2$ values of $8.07{\pm}0.84$ and $7.93{\pm}0.11$, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac ?${\beta}-adrenoceptors$. YS 49, YS 51, and higenamine showed ?${\alpha)-adrenoceptor$ affinity in rat brain, in which the dissociation constant $(K_i)$ was 2.75, 2.81, and 1.02 ${\mu}M$, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to ${\alpha)_1-adrenoceptor$ in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac ${\beta}-adrenoceptors$. Thus, these chemicals may be useful in the treatment of congestive heart failure.

• The Korean Journal of Pain
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• v.21 no.3
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• pp.179-186
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• 2008

Background: The adrenergic nervous system in the spinal cord contributes to the development of neuropathic pain after nerve injury. Brain derived neurotrophic factor may facilitate the sympathetic change in the spinal cord and influence the state of neuropathic pain. We probed the effect of chronic repetitive administration of systemic 4-methylcatechol, which is known to be a neurotrophic factor inducer, in a spinal nerve ligation model. Methods: We made the rat neuropathic pain model by the ligation of the L5 spinal nerve. Intraperitoneal 4-methylcatechol ($10{\mu}g/kg$) or the same volume of saline wasadministrated twice daily just after the operation for 7 days. The tactile allodynia was measured by using von Frey filaments and its change was followed up from 3 days after SNL. The lumbosacral enlargement of the spinal cord was taken out and the mRNA contents of the ${\alpha}_2-adrenoceptor$ subtypes were measured by real time polymerase chain reaction and this was then compared with the control groups. The antiallodynic effect of intrathecal clonidine (3, 10, $30{\mu}g$) was evaluated and compared in the 4-methylcatechol treated rats and the control rats. Results: The expression of the ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptor subtypes did not change after 4-methylcatechol treatment. Intrathecal clonidine showed an earlier and better effect at the highest dose ($30{\mu}g$ intrathecal), but not with any other doses. Conclusions: Chronic intraperitoneal administration of 4-methylcatechol may improve the effect of intrathecal clonidine, but we could not prove the increase of ${\alpha}_{2A}$ and ${\alpha}_{2C}$ adrenoceptors in the spinal cord of 4-methylcatechol treated rats.

• The Korean Journal of Pharmacology
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• v.20 no.2
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• pp.59-71
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• 1984

To explore the regulatory roles of CNS on the renal function, clonidine, a specific presynaptic ${\alpha}-adrenoceptor$ agonist, was administered into a lateral ventricle of the brain (icv) and the changes of renal function were studies in urethane-anesthetized rabbits. $5{\mu}g/kg$ icv elicited no significant changes in renal function. However, $15{\mu}g/kg$ induced marked natriuresis and kaliuresis for 20 min. Neither RPF nor GFR changed significantly. The fractional sodium reabsorption was significantly reduced, indicating that the renal action was of the tubular origin. Changes of systemic blood pressure were not contributory to the renal action. Yohimbine, a specific antagonist for presynaptic ${\alpha}-adrenoceptor$, when given icv in doses of $100{\mu}g/kg$ 20 min prior to clonidine, completely abolished the renal action of icv clonidine. Yohimbine icv did not produce any significant changes in renal function. Intravenous clonidine, $15{\mu}g/kg$, elicited antidiuresis and decrement of renal function immediately after administration, followed by a slight tendency toward natriuresis, but no natriuresis corresponding to those seen after the icv clonidine were observed, indicating that in the renal action of icv clonidine no direct action is involved. These observations indicate that the central sympathetic tone plays a role in the regulation of renal function in the rabbit.

• Journal of Life Science
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• v.10 no.6
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• pp.584-590
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• 2000

Natural products are one of the useful source of cardiovascular drugs, in particular, when they have antioxidant activity. Gagaminine, an alkaloid isolated from the roots of Cynanchum wilfordi Hemsley, has been reported to potently inhibit the aldehyde oxidase activity ({TEX}$IC_{50}${/TEX}=0.8$\mu$M) and reduce lipid peroxidation. However, the effect of gagaminine on vascular smooth muscle has not yet been investigated. In the present study, we examined whether gagaminine relaxes vascular smooth muscle by isometric tension study. In order to observe its relaxation effect on the arteries, conductivel vessel (rat thoracic aorta) and resistance vessel (pig coronary artery) were purposely used. Results indicated that gagaminine relaxed in a concentration-dependent manner $\alpha$-adrenoceptor agonist, phenylephrine (PE)-induced contraction of rat aorta. Pretreatment with gagaminine inhibited PE-induced contraction, noncompetitively. {TEX}$Ca^{2+}${/TEX}-induced contraction was significantly diminished by gagaminine. In pig coronary artery, gagaminine relaxed thromboxane receptor (U 46619)-mediated contraction in dose-dependent manner. Pretreatment with gagaminine also reduced the maximum contraction induced by KCl. These observations strongly suggest that agagminnine relaxes vascular smooth muscle, irrespective of both resistance and conductive artery. We demonstrate that gagaminine, a potent natural antioxidant, has a significant vasodilatory effect and its action mechanism van be ascribed at least in part to {TEX}$Ca^{2+}${/TEX} antagonistic action as evidenced by inhibition {TEX}$Ca^{2+}${/TEX}-induced contraction (rat aorta) and KCl-induced contraction (porcine artery). Furthermore, neither $\alpha$ -adrenoceptor nor thromboxane receptor seems responsible for the relaxation of gagaminine.

• The Journal of Korean Medicine
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• v.25 no.3
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• pp.67-77
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• 2004

Objectives : Many studies have reported that acupuncture analgesia was mediated through the activation of peripheral and central opioid receptors. However, there has been little electrophysiological study on the adrenergic mechanism of acupuncture analgesia in chronic inflammatory and neuropathic pain. The present study was undertaken to elucidate the role of adrenoceptors in the production of acupuncture analgesia in the chronic pain model. Methods : In the rat with chronic inflammation and nerve injury, dorsal horn cell (DHC) responses to afferent C fiber stimulation were used as a pain index and changes in electroacupuncture (EA) analgesia were recorded before and after intravenous administration of selective adrenoceptor antagonists. EA stimulations (2Hz, 0.5msec, 3mA) were applied to the contralateral Zusanli point for 30 min. Results : EA stimulation induced long-lasting inhibition of DHC responses in the rat with chronic inflammation and nerve injury. In both models of inflammation and neuropathic pain, α-adrenoceptor antagonist (phentolamine) significantly attenuated an inhibitory effect of EA on DHC responses. Selective α2-adrenoceptor antagonist (yohimbine) also had a similar suppressive action on DHC responses to that of phentolamine. However, β-adrenoceptor antagonist (propranolol) did not have any inhibitory effect on DHC responses in either model of chronic pain. Conclusions : These experimental findings suggest that in rats with chronic pain, EA stimulation with low frequency and high intensity produced an analgesic effect which was mediated through an activation of α2-adrenoceptors.