• The Korean Journal of Pharmacology
• /
• v.20 no.2
• /
• pp.7-14
• /
• 1984

In pithed rats, rising in diastolic blood pressure by clonidine, when intravenously injected, is expressed as the postsynaptic action, and inhibitory action on electrical stimulation-induced tachycardia by clonidine is expressed as the presynaptic inhibitory action. In this study it was aimed to observe the inhibitory effect of imipramine caused by a single and chronic administration on both postsynaptic and presynaptic action of clonidine in pithed rats, and discussed in relation with the mechanism of antidepressant action of imipramine. 1) A rise of diastolic blood pressure by clonidine was not antagonized by prazosin, but by both phentolamine and piperoxan. 2) The inhibition by clonidine of tachycardia which was induced by electrical stimulation was also antagonized by phentolamine and piperoxan, but not by prazosin. 3) The increase in diastolic blood pressure in response to clonidine was inhibited by both a single or chronic administration with imipramine (20 mg/kg). It was more pronounced in the latter. 4) The inhibitory action of clonidine on the tachycardia was markedly inhibited by both types of administration with imipramine, between which there showed little difference. It is concluded that the presynaptic ${\alpha}_2-adrenoceptor$ is rather sensitively affected by a single administration with imipramine, and a long-term imipramine treatment may inhibit both pre- and postsynaptic ${\alpha}_2-adrenoceptors$, simultaneously. Furthermore, it was seemed unlikely that these results provide the evidence :to support the fact that the subsensitivity of presynaptic ${\alpha}_2-adrenoceptor$ may be the mechanism of action of tricyclic antidepressant.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.5
• /
• pp.495-507
• /
• 2017

The effect of clonidine administered intrathecally (i.t.) on the mortality and the blood glucose level induced by sepsis was examined in mice. To produce sepsis, the mixture of D-galactosamine (GaLN; 0.6 g/10 ml)/lipopolysaccharide (LPS; $27{\mu}g/27{\mu}l$) was treated intraperitoneally (i.p.). The i.t. pretreatment with clonidine ($5{\mu}g/5{\mu}l$) increased the blood glucose level and attenuated mortality induced by sepsis in a dose-dependent manner. The i.t. post-treatment with clonidine up to 3 h caused an elevation of the blood glucose level and protected sepsis-induced mortality, whereas clonidine post-treated at 6, 9, or 12 h did not affect. The pre-treatment with oral D-glucose for 30 min prior to i.t. post-treatment (6 h) with clonidine did not rescue sepsis-induced mortality. In addition, i.t. pretreatment with pertussis toxin (PTX) reduced clonidine-induced protection against mortality and clonidine-induced hyperglycemia, suggesting that protective effect against sepsis-induced mortality seems to be mediated via activating PTX-sensitive G-proteins in the spinal cord. Moreover, pretreatment with clonidine attenuated the plasma tumor necrosis factor ${\alpha}$ ($TNF-{\alpha}$) induced by sepsis. Clonidine administered i.t. or i.p. increased $p-AMPK{\alpha}1$ and $p-AMPK{\alpha}2$, but decreased p-Tyk2 and p-mTOR levels in both control and sepsis groups, suggesting that the up-regulations of $p-AMPK{\alpha}1$ and $p-AMPK{\alpha}2$, or down-regulations of p-mTOR and p-Tyk2 may play critical roles for the protective effect of clonidine against sepsis-induced mortality.

• The Korean Journal of Pain
• /
• v.8 no.2
• /
• pp.286-292
• /
• 1995

Buerger's disease(Thromboangiitis Obliterans) is characterized by peripheral arterial occlusion of the extremities in young smokers, and leading to ischemia of the tissue and gangrene. Most of these patients suffered from severe pain. therapy for Buerger's disease not enable to undergo reconstructive arterial surgery has been discouraging while multiple modes of analgesics have advanced. Eight subjects who had been operated due to Buerger's disease or diagnosed with this disease were evaluated retrospectively. Continuous epidural block was done at L 2~3 or L3~4 intervertebral space and multiday continuous infusor was connected to epidural catheter. The content of the infusor was clonidine-bupivacaine or clonidine-morphine-bupivacaine mixture. The minimum dose of clonidine was 75 ${\mu}g/day$ and the maximum 450 ${\mu}g/day$. The results were as follows: The analgesia produced by clonidine was superior to any other analgesics. 2) The incidence of the side effects produced by clonidine-bupivacaine mixture were less than that of clonidine-morphine-bupivacaine mixture. 3) Minimum dose of clonidine for the pain relief was required more than 225 ${\mu}g$ per day. From the above results, we recommend that clonidine is an effective agent to provide pain relief for the patients with Buerger's disease.

• Archives of Pharmacal Research
• /
• v.9 no.4
• /
• pp.219-222
• /
• 1986

Dose-dependent increasesin blood glucose were produced by epinephrine and clonidine in fasted male mice. Isoproterenol was ineffective in increasing blood glucose at lower doses ($10^{-8}M$/kg-$10^{-7}M$/kg); with higher dose ($10^{-6}M$/kg) the glucose level was increased. The hyperglycemia induced by epinephrine was inhibited by yobimbine, prazosin and propranolol, indicating that the hyperglycemic effect of epinephrine is mediated by alpha-1, alpha-2 and beta adrenoceptor. When clonidine (10$^{-6}$ M/kg) was administered simultaneously with sioproterenol ($10^{-6}M$/kg), an enhenced hyperglycemic effect was observed. The increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These increment produced by clonidine plus isoproterenol was higher than that by clonidine alone. These results suggest that stimulation of alpha-2 adrenoceptor may be reponsible for the exertion of the hyperglycemic effect by beta agonists in fasted mice.

• YAKHAK HOEJI
• /
• v.31 no.2
• /
• pp.82-91
• /
• 1987

The effect of neurotoxic compound 6-hydroxydopamine (6-OHDA) on the change in blood pressure and contractile response of Vas deference by centrally acting agents has been studied in normal and DOCA-salt induced hypertensive rats. The treatment of neonatal rats with 6-OHDA (2$\times$100mg, 250mg Kg$^{-1}$s.c) significantly inhibited the antihypertensive and relaxant effects of Vas deference of clonidine(100$\mu\textrm{g}$ Kg$^{-1}$iv.). The simultaneous administration of desipramine with clonidine into neonatal rats decreased the antihypertensive response of clonidine although treated did not affect the relaxative response of Vas deference. Furthermore, the antihypertensive and relaxant responses of clonidine were reduced by the neonatal rats with 6-OHDA regardless of the administration of desipramine. When neonatal rats were administered with 6-OHDA, the development of DOCA-salt hypertension was prevented. These results suggest that 6-OHDA, clonidine and desipramine hada significant effect on the development and the inhibition of central hypertension mediating the central adrenergic neuron due to their affinity to the central nervous system.

• YAKHAK HOEJI
• /
• v.26 no.2
• /
• pp.105-110
• /
• 1982

The antihypertensive effect of clonidine administered concurrently with labetalol or metoprolol were studied with spontaneously hypertensive rats (SHR). The changes of heart rate were also observed in the same rats. Every drug was orally administered single dose after prechecking the systolic blood pressure and heart rate of SHR. The blood pressure of SHR in concurrently administered group was more significantly decreased than in alone administered group. The effective and stable decrease of blood pressure was maintained at the group of clonidine with labetalol (0.05+50mg/kg) for 9 hours. The group of clonidine with metoprolol (0.05+100mg/kg) manifested more marked decrease of blood pressure than the group of metoprolol (100mg/kg) alone for 9 hours. The diminishing effect of heart rate was enhanced in group of administering clonidine with labetalol, decreasing the dose of labetalol from 50mg/kg via 25mg/kg to 12.5mg/kg. On the other hand, in the group that clonidine was administered concurrently with metoprolol, the diminishing effect of heart rate was decreased with decreasing doses of metoprolol from 100mg/kg via 50mg/kg to 25mg/kg.

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

• The Korean Journal of Pain
• /
• v.14 no.1
• /
• pp.41-45
• /
• 2001

Background: Clonidine, a selective ${\alpha}_2$ adrenergic agonist, increases the duration of anesthesia and analgesia when it is used with local anesthetics. This study was undertaken to evaluate whether clonidine, which was mixed with lidocaine for the brachial plexus block (BPB), has a local (peripheral) or a systemic (central) anesthetic effect. Methods: Seventy patients scheduled for upper extremity surgery were randomly allocated to two groups. In group IV (n = 35) an axillary perivascular BPB was performed with 40 ml of 1% lidocaine and 1：200,000 epinephrine, and just after BPB clonidine $2{\mu}g/kg$ was administered intravenously. In group BPB (n = 35) the same BPB was performed with 40 ml of 1% lidocaine, 1：200,000 epinephrine and clonidine $2{\mu}g/kg$. The following variables were recorded: onset time, duration of anesthesia and analgesia, and adverse effects. Results: Onset time was comparable in both groups. The duration of anesthesia and analgesia significantly increased to 306 min and 354 min in group BPB, when compared to 119 min and 151 min in group IV, respectively. No side effects such as hypotension, bradycardia, and sedation were reported. Conclusions: The duration of anesthesia and analgesia is prolonged by adding clonidine to lidocaine during brachial plexus block, which suggests that its effect is local rather than systemic.

• The Korean Journal of Physiology
• /
• v.21 no.1
• /
• pp.67-77
• /
• 1987

Effect of intravenously injected clonidine on the flexion reflex was studied in 15 decerebrated and spinalized cats. The flexion reflex was elicited by electrical stimulation of the tibial nerve or the common peroneal nerve and it was recorded as single unit activity from filaments of the L6 or L7 ventral roots. In order to obtain the late flexion reflex discharges, $A{\delta}$ and C afferent fibers were stimulated with single or train electrical pulses respectively. The flexion reflex, especially the late component, was markedly inhibited after intravenous administration of clonidine. The clonidine-induced inhibition of the flexion reflex was compared before and after treatment of the animals respectively with yohimbine and naloxone. The inhibitory effect on the flexion reflex of clonidine was not altered by naloxone, a ${\mu}-opioid$ receptor blocker, whereas it was completely blocked by yohimbine, an ${\alpha}_2-adrenergic$ antagonist. These results indicate that clonidine inhibits the flexion reflex through excitation of ${\alpha}_2-adrenoceptors$ even at the spinal cord level.

• Archives of Pharmacal Research
• /
• v.11 no.1
• /
• pp.65-73
• /
• 1988

The effects of clonidine on the negative chronotropic response induced by stimulation of vagus nerve were studied in the presence of propranolol in reserpinized and anesthetized rats. When the heart rate was decreased by stimulation of the vagus nerve, clonidine significantly inhibited vagally induced heart rate decrease (negative chronotropic response) in dose dependent manner. This inhibitory effect of clonidine was virtually abolished by phentolamine, ${\alpha}_1-\;and\;{\alpha}_2-adrenoceptor$ antagonist, and partially antagonized by prazosin, ${\alpha}_1-adrenoceptor$ antagonist. On the other hand, when the heart rate was decreased by the infusion of bethanechol, a muscarinic parasympathetic stimulant, clonidine had no effect on the bethanechol-induced heart rate decrease. These results suggest that clonidine inhibits vagally induced negative chronotropic response by activation of presynaptic ${\alpha}-adrenoceptors$ located on the parasympathetic cholinergic nerve terminal in the heart and this effect of clonidine is more related to ${\alpha}_2-adrenoceptors$ than ${\alpha}_1-adrenoceptors$.