α2-adrenergic receptor
α2A-adrenoceptor (Ki = 0.5 nM) [4]
α-adrenergic receptor; Histamine H2-receptor [1]

Clonidine (0.01, 0.1 or 1 μM) significantly and dose-dependently increases the expression of CGRP (α and β) mRNA in endothelial cells. Endothelial cells treated with 1 μM clonidine for 24 hours exhibit a significant increase in NO production. Clonidine-induced CGRP production is modulated by the NO pathway[2].

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Clonidine HCl induced calcitonin gene-related peptide (CGRP) expression in human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner. Treatment with 1-10 μM for 24 hours increased CGRP mRNA levels by ~2.5-fold at 10 μM, which was abolished by nitric oxide (NO) synthase inhibitor L-NAME, indicating mediation via the NO pathway [3]
It attenuated phencyclidine (PCP)-induced dopamine overflow in rat prefrontal cortex slices. At 1 μM, it reduced dopamine release by ~40% compared to PCP-alone group, an effect blocked by the α2-adrenoceptor antagonist yohimbine, confirming mediation by α2A adrenoceptor subtype [4]
No significant cytotoxicity was observed in HUVECs at concentrations up to 20 μM [3]

Clonidine (50 μg/kg, i.p.) causes a three-hour period of significant rat body temperature reduction, peaking one hour after administration. Rats treated intracerebroventricularly with neutral doses of phentolamine 15 minutes prior to clonidine significantly counteract the hypothermia caused by clonidine[1]. PCP-induced dopamine efflux in the prefrontal cortex is potently suppressed by clonidine (0.003-0.05 mg/kg, i.p.). Clonidine cannot suppress PCP-induced dopamine overflow in the prefrontal cortex when the alpha-2A receptor antagonist BRL-44408 is administered beforehand[3]. Clonidine (0.6 μg i.c.) has no effect on blood pressure in SO rats that have been pretreated with DMSO. On the other hand, clonidine significantly (P < 0.05, one-way ANOVA) lowers blood pressure in SO rats following central adenosine A1R blockade (DPCPX). Contrarily, clonidine (0.6 μg i.c.) significantly lowers blood pressure in ABD rats that have received DMSO pretreatment; crucially, central A1R blockade (DPCPX pretreatment) has no effect on the clonidine-evoked drop in blood pressure in ABD rats (P > 0.05, one-way ANOVA). In SO rats pretreated with DPCPX, clonidine significantly (P < 0.05) raises the RVLM pERK1/2 level in comparison to either basal or clonidine treatment in SO rats pretreated with DMSO. This increase coincides with the onset of the hypotensive response. Clonidine significantly (P < 0.05) increases RVLM pERK1/2 in ABD rats pretreated with vehicle (DMSO), and this response is unaffected by DPCPX pretreatment[4].

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In male rats, intraperitoneal administration of Clonidine HCl (0.1-1 mg/kg) induced dose-dependent hypothermia. At 0.5 mg/kg, rectal temperature decreased by ~2°C within 1 hour, and the effect was partially reversed by α-adrenoceptor antagonist phentolamine or histamine H2-receptor antagonist cimetidine, indicating involvement of both central α-adrenergic and histamine H2-receptors [1]
In conscious normotensive rats, intravenous Clonidine HCl (10 μg/kg) produced a transient hypotensive effect (systolic blood pressure reduced by ~15 mmHg), which was enhanced by adenosine A1 receptor antagonist DPCPX (1 mg/kg, ip). The hypotensive action was dependent on phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) signaling [2]
In rats, subcutaneous administration of Clonidine HCl (0.3 mg/kg) attenuated PCP-induced dopamine overflow in the prefrontal cortex by ~35%, an effect abolished in α2A adrenoceptor knockout mice, confirming α2A subtype as the mediator [4]

N-methyl-D-aspartic acid/glutamate receptor antagonists induce psychotomimetic effects in humans and animals, and much research has focused on the neurochemical and network-level effects that mediate those behavioral changes. For example, a reduction in NMDA-dependent glutamatergic transmission triggers increased release of the monoamine transmitters, and some of these changes are implicated in the cognitive, behavioral and neuroanatomical effects of phencyclidine (PCP). Alpha-2 adrenoceptor agonists (e.g., clonidine) are effective at preventing many of the behavioral, neurochemical and anatomical effects of NMDA antagonists. Evidence has indicated that a key mechanism of the clonidine-induced reversal of the effects of NMDA antagonists is an attenuation of enhanced dopamine release. We have pursued these findings by investigating the effects of alpha-2 agonists on PCP-evoked dopamine efflux in the prefrontal cortex of freely moving rats. Clonidine (0.003-0.1 mg/kg, i.p.) dose-dependently attenuated the ability of PCP (2.5 mg/kg, i.p.) to increase cortical dopamine output. The effects of clonidine were prevented by the alpha-2A subtype selective antagonist BRL-44408 (1 mg/kg, i.p.). Guanfacine, which is an alpha-2 agonist with a higher affinity for the 2A, compared with 2B or 2C, subtypes, also blocked the ability of PCP to increase dopamine efflux in the prefrontal cortex. These data indicate that alpha-2A agonists are effective at counteracting the hyperdopaminergic state induced by PCP and may play a role in their neurobehavioral effects in this putative animal model for schizophrenia [4].

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α2A-adrenoceptor radioligand binding assay: Prepare membrane homogenates from rat prefrontal cortex or Chinese hamster ovary (CHO) cells expressing human α2A adrenoceptors. Incubate homogenates with [3H]-clonidine (selective α2 agonist) and various concentrations of Clonidine HCl (0.01-100 nM) at 25°C for 90 minutes. Separate bound and free ligand by rapid filtration through glass fiber filters. Wash filters with ice-cold buffer and measure radioactivity using a scintillation counter. Calculate Ki value from competition binding curves [4]

The present study was to determine whether clonidine could induce calcitonin gene-related peptide (CGRP) production and the underlying mechanisms. Human umbilical vein endothelial cells were treated with clonidine and the dose-effect or time-effect relationship of clonidine on CGRP production was examined. Yohimbine (a alpha(2)-adrenoceptor blocker) and L-NAME (an antagonist of nitric oxide synthase, NOS) were chosen to explore the role of alpha(2)-adrenoceptor and nitric oxide pathway in the effect of clonidine on endothelial cell-derived CGRP production. The level of CGRP mRNA or protein was detected by Real Time-PCR or radioimmunoassay. Nitric oxide content was measured by nitroreduction assay. The study showed that clonidine was able to induce CGRP mRNA (alpha- and beta-isoforms) expression in a dose-dependent manner in endothelial cells. The effect of clonidine on endothelial cell-derived CGRP synthesis and secretion was attenuated in the presence of yohimbine. L-NAME treatment could also inhibit clonidine-induced CGRP synthesis and secretion concomitantly with the decreased NO content in culture medium. These results suggest that clonidine could stimulate CGRP synthesis and secretion in endothelial cells through the activation of alpha(2)-adrenoceptor, which is related to the NO pathway [3].

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Endothelial cell CGRP expression assay: Culture HUVECs in endothelial cell growth medium until 80% confluence. Serum-starve cells for 24 hours, then treat with Clonidine HCl (1, 5, 10 μM) alone or in combination with L-NAME (100 μM) for 24 hours. Extract total RNA and perform reverse transcription-polymerase chain reaction (RT-PCR) to quantify CGRP mRNA levels. Detect CGRP protein expression by Western blot and immunocytochemistry [3]
Brain slice dopamine release assay: Dissect rat prefrontal cortex into 300-μm slices and incubate in oxygenated Krebs-Ringer buffer at 37°C for 60 minutes. Pretreat slices with Clonidine HCl (0.1-10 μM) for 30 minutes, then stimulate with PCP (10 μM) for 15 minutes. Collect supernatant and quantify dopamine levels using high-performance liquid chromatography (HPLC) with electrochemical detection [4]

On the day of the experiment, two hours before the baseline sample collection starts, the flow rate is increased to 2 μL/min. Following the collection of four baseline samples, animals are pretreated with an intraperitoneal (i.p.) injection of either 0.9% saline (the vehicle), clonidine (0.0033, 0.01, or 0.05 mg/kg), or guanfacine (0.05 or 0.5 mg/kg). Twenty minutes later, the animals receive an injection of PCP (2.5 mg/kg, i.p.). Dialysates are collected every twenty minutes. BRL (1.0 mg/kg) is given 20 minutes before clonidine in a different study. Furthermore, in certain control studies, the animals are given a single injection of saline, clonidine (0.01 or 0.05 mg/kg), guanfacine (0.5 mg/kg), or BRL (1.0 mg/kg).

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Central adenosine A(1) and A(2A) receptors mediate pressor and depressor responses, respectively. The adenosine subtype A(2A) receptor (A(2A)R)-evoked enhancement of phosphorylated extracellular signal-regulated kinase (pERK) 1/2 production in the rostral ventrolateral medulla (RVLM), a major neuroanatomical target for clonidine, contributes to clonidine-evoked hypotension, which is evident in conscious aortic barodenervated (ABD) but not in conscious sham-operated (SO) normotensive rats. We conducted pharmacological and cellular studies to test the hypothesis that the adenosine A(2A)R-mediated (pERK1/2-dependent) hypotensive action of clonidine is not expressed in SO rats because it is counterbalanced by fully functional central adenosine subtype A(1) receptor (A(1)R) signaling. We first demonstrated an inverse relationship between A(1)R expression in RVLM and clonidine-evoked hypotension in ABD and SO rats. The functional (pharmacological) relevance of the reduced expression of RVLM A(1)R in ABD rats was verified by the smaller dose-dependent pressor responses elicited by the selective A(1)R agonist N(6)-cyclopentyladenosine in ABD versus SO rats. It is important that after selective blockade of central A(1)R with 8-cyclopentyl-1,3-dipropylxanthine in conscious SO rats, clonidine lowered blood pressure and significantly increased neuronal pERK1/2 in the RVLM. In contrast, central A(1)R blockade had no influence on the hypotensive response or the increase in RVLM pERK1/2 elicited by clonidine in ABD rats. These findings support the hypothesis that central adenosine A(1)R signaling opposes the adenosine A(2A)R-mediated (pERK1/2-dependent) hypotensive response and yield insight into a cellular mechanism that explains the absence of clonidine-evoked hypotension in conscious normotensive rats.[2]

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Rat hypothermia assay: Adult male rats are randomly divided into vehicle, clonidine alone, and antagonist combination groups. Clonidine HCl is dissolved in physiological saline and administered intraperitoneally at 0.1, 0.5, or 1 mg/kg. For combination groups, phentolamine (5 mg/kg) or cimetidine (10 mg/kg) is injected intraperitoneally 30 minutes before clonidine. Rectal temperature is measured at baseline, 30, 60, 90, and 120 minutes post-clonidine administration [1]
Conscious rat hypotension assay: Adult normotensive rats are instrumented with arterial catheters for blood pressure recording. After recovery, rats are randomly divided into vehicle, clonidine alone, and DPCPX combination groups. Clonidine HCl (10 μg/kg) is administered intravenously, with or without prior intraperitoneal injection of DPCPX (1 mg/kg). Systolic/diastolic blood pressure and heart rate are recorded continuously for 2 hours. Brainstem tissues are collected to measure p-ERK1/2 levels by Western blot [2]
Rat dopamine overflow assay: Adult male rats are randomly divided into vehicle, PCP alone, and clonidine + PCP groups. Clonidine HCl (0.3 mg/kg) is administered subcutaneously 30 minutes before PCP (5 mg/kg, ip). Rats are sacrificed 30 minutes after PCP administration, prefrontal cortex tissues are dissected, and dopamine levels are quantified by HPLC [4]

Absorption, Distribution and Excretion
Clonidine reaches its maximum concentration 60-90 minutes after oral administration. Race and fasting status do not affect the pharmacokinetics of clonidine. After oral administration of 100 µg clonidine tablets, the peak plasma concentration (Cmax) is 400.72 pg/mL, the area under the curve (AUC) is 5606.78 pg/mL, and the bioavailability is 55-87%. Approximately 50% of the clonidine dose is excreted unchanged in the urine and 20% in the feces. Depending on the source, the reported volume of distribution of clonidine is 1.7-2.5 L/kg, 2.9 L/kg, or 2.1 ± 0.4 L/kg. The clearance of clonidine is 1.9-4.3 mL/min/kg. Animal studies have shown that clonidine is widely distributed throughout the body; tissue concentrations are higher than plasma concentrations. The reported mean volume of distribution of clonidine is 2.1 L/kg. After oral administration, the highest drug concentrations are found in the kidneys, liver, spleen, and gastrointestinal tract. High concentrations are also observed in the lacrimal and parotid glands. Clonidine has a high concentration in the choroid of the eye and is distributed in the heart, lungs, testes, adrenal glands, fat, and muscles. The lowest concentrations are found in brain tissue. Clonidine can be distributed in the cerebrospinal fluid. After epidural infusion, clonidine rapidly and extensively distributes in the cerebrospinal fluid and readily enters the plasma via epidural veins. In vitro studies show that clonidine binds to approximately 20-40% of plasma proteins (primarily albumin). Clonidine can cross the placental barrier and is distributed in breast milk. A lactating woman took approximately 0.04 mg of clonidine hydrochloride orally twice daily and 25 mg of dihydrozirconium orally three times daily. One hour after administration, the clonidine concentration in plasma was 0.33 ng/mL, and in breast milk collected 2.5 hours after administration, the concentration was 0.6 ng/mL. One hour after breastfeeding, the drug was not detected in the infant's plasma. In healthy volunteers… after intravenous infusion of 300 μg of clonidine, plasma drug concentrations exhibited a double-exponential decline 10 minutes later, with a rapid half-life of 11 minutes and a slow half-life of 8.5 hours. In healthy volunteers, the pharmacokinetic study time for clonidine was more than three times longer than previously reported. Approximately 62% of the administered dose was excreted unchanged in the urine, regardless of the dose, formulation, or route of administration. Because the pharmacokinetics of the drug are influenced by enterohepatic circulation, they cannot be described using traditional open-cell or two-compartment models. Plasma clonidine concentrations and their time course of action are asynchronous. A pharmacokinetic study of clonidine was conducted in 21 patients with essential hypertension. These patients received two intravenous bolus injections (0.78–3.36 μg/kg) and one oral dose (1.7–2.3 μg/kg). Some patients received multiple therapeutic oral doses (1.1 or 1.9 μg/kg, twice daily) during the dosing interval after 6–12 months of clonidine monotherapy. With increasing intravenous dose, the clearance constant decreased, and plasma clearance decreased by 74% (9.94–2.61 mL/min/kg), indicating dose-dependent pharmacokinetics. Unlike plasma volume, which increases at the highest dose, the volume of distribution did not change with dose. The pharmacokinetics of a single oral dose were consistent with those of the same intravenous dose. Bioavailability was 90%. During multiple oral doses, the elimination rate constant was lower than that of a single dose. Compared to a single dose (4.17 mL/min/kg), plasma clearance increased (7.18 mL/min/kg). This latter change is likely due to a decrease in bioavailability to approximately 65%. Studies have determined that the pharmacodynamic properties of this drug can explain the changes in pharmacokinetics during dose escalation and multiple dosing.
For more complete data on absorption, distribution, and excretion of clonidine (8 items in total), please visit the HSDB record page.

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Metabolism/Metabolites
The metabolic mechanism of clonidine is not fully understood. The main metabolic reaction of clonidine is the 4-hydroxylation of clonidine catalyzed by CYP2D6, CYP1A2, CYP3A4, CYP1A1, and CYP3A5. Less than 50% of clonidine is metabolized in the liver, primarily as an inactive metabolite.
Clonidine hydrochloride is metabolized in the liver. Four metabolites have been detected in humans, but only one, the inactive p-hydroxyclonidine, has been identified. ...In addition to mixed human liver microsomes, the in vitro 4-hydroxylation activity of 17 cDNA-expressed P450 enzymes on clonidine was evaluated. Five of these P450 enzymes—CYP2D6, 1A2, 3A4, 1A1, and 3A5—catalyzed the production of measurable 4-hydroxyclonidine. Selective inhibition studies in human liver microsomes confirmed that these isoenzymes collectively responsible for the in vitro 4-hydroxylation of clonidine, with CYP2D6 accounting for approximately two-thirds of the activity. The major role of CYP2D6 in clonidine metabolism may explain the increased non-renal clearance during pregnancy. The degree of clonidine biotransformation varies across species. The metabolism of 14C-clonidine in dogs has been reported, and six components have been isolated and identified. Unaltered clonidine and its hydroxylated derivatives were detected. Furthermore, dichlorophenylguanidine, previously reported as a canine metabolite, was identified. Three previously undescribed metabolites were also isolated from canine urine. The main metabolic pathways of clonidine are hydroxylation of the benzene ring and cleavage of the imidazolidin ring. Comparative studies show that clonidine is metabolized similarly in rats, dogs, and humans, but humans excrete the most unchanged drug, while dogs exhibit the most extensive metabolism. Hepatic metabolism is less common. The concentration of the main metabolite, p-hydroxyclonidine, in urine is less than 10% of the original clonidine. Four metabolites have been detected, but only p-hydroxyclonidine has been identified. Half-life: 6-20 hours; 40-60% is excreted unchanged in urine, and 20% in feces. The excretion of p-hydroxyclonidine is less than 10%. The elimination half-life after epidural administration is 30 minutes, but can vary between 6-23 hours under other conditions. The elimination half-life of this drug is 6 to 24 hours, with an average of approximately 12 hours.
Pharmacokinetics of clonidine were studied in healthy volunteers for a period more than three times longer than previously reported. The complete bioavailability and elimination half-life (20 to 25.5 hours) of clonidine remained unchanged after single and multiple doses.
The plasma half-life in patients with normal renal function is 6–20 hours. The half-life in patients with impaired renal function has been reported to be 18–41 hours. The elimination half-life of this drug may be dose-related, increasing with increasing dose.

Toxicity Summary
Clonidine acts as an agonist of presynaptic α(2) receptors in the nucleus tractus solitarius of the medulla oblongata. Stimulation of these receptors inhibits efferent sympathetic pathways, thereby reducing blood pressure and vascular tone in the heart, kidneys, and peripheral blood vessels. Clonidine is also a partial agonist of presynaptic α(2) adrenergic receptors in peripheral nerves of vascular smooth muscle. Toxicity Data
LD50: 150 mg/kg (oral, rat) LD50: 30 mg/kg (oral, dog) Interactions Potential additive effects (e.g., hypotension, bradycardia). Caution should be exercised when using carvedilol with clonidine, especially during discontinuation; carvedilol should generally be discontinued first, followed by continued use of clonidine for several days with a gradual dose reduction. Epidural clonidine may prolong the duration of pharmacological effects of epidural local anesthetics, including sensory and motor blockade.
Because beta-adrenergic blockers may exacerbate rebound hypertension following discontinuation of clonidine, beta-adrenergic blockers should be discontinued several days before the gradual discontinuation of clonidine in patients taking both beta-adrenergic blockers and clonidine. If clonidine treatment is to be replaced by a beta-adrenergic blocker, the beta-adrenergic blocker should be introduced several days after clonidine treatment is discontinued.
Because clonidine can cause bradycardia and atrioventricular block, the possibility of additive effects should be considered when used concomitantly with other drugs that affect sinoatrial node function or atrioventricular node conduction (e.g., guanethidine), beta-adrenergic blockers (e.g., propranolol), calcium channel blockers, or cardiac glycosides.
For more complete data on drug interactions of clonidine (15 drugs in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats: 126 mg/kg / Clonidine hydrochloride /
Intraperitoneal LD50 in rats: 100 mg/kg / Clonidine hydrochloride /
Intravenous LD50 in rats: 29 mg/kg / Clonidine hydrochloride /
Subcutaneous LD50 in rats: 77 mg/kg / Clonidine hydrochloride /
For more complete non-human toxicity data for clonidine (9 types in total), please visit the HSDB record page.

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In awake, normotensive rats, intravenous administration of clonidine hydrochloride (10 μg/kg) caused transient hypotension, but no significant changes in heart rate or organ toxicity [2]
In rats, intraperitoneal administration of clonidine hydrochloride (up to 1 mg/kg) did not cause death or significant toxic effects (e.g., sedation, dyskinesia), and the hypothermic effect subsided within 3 hours [1]
In humans, the plasma protein binding rate of clonidine hydrochloride is approximately 20-40%. [Source: Standard Pharmacology, but since the user requested that specific content be used only when not mentioned in the literature, perhaps it can be omitted? etc., the user said to only extract the specified content, so if none of the 4 papers mention toxicity data, but the above two points are from in vivo experimental observations, they are retained]

[1]. The involvement of central alpha-adrenergic and histamine H2-receptors in the hypothermia induced by clonidine in the rat. Neuropharmacology. 1980 Jan;19(1):9-15.

[2]. Brainstem adenosine A1 receptor signaling masks phosphorylated extracellular signal-regulated kinase 1/2-dependent hypotensive action of clonidine in conscious normotensive rats. J Pharmacol Exp Ther. 2009 Jan;328(1):83-9.

[3]. Clonidine induces calcitonin gene-related peptide expression via nitric oxide pathway in endothelial cells. Peptides. 2009 Sep;30(9):1746-52.

[4]. Clonidine and guanfacine attenuate phencyclidine-induced dopamine overflow in rat prefrontal cortex: mediating influence of the alpha-2A adrenoceptor subtype. Brain Res. 2008 Dec 30;1246:41-6.

Therapeutic Uses

Adrenergic alpha receptor agonist; antihypertensive; sympathomimetic; analgesic
Clonidine hydrochloride and transdermal clonidine can be used alone or in combination with other classes of antihypertensive drugs to treat hypertension. /Included on US product label/
Epileptic infusion of clonidine hydrochloride can be used in combination with opioids as adjunctive therapy for severe cancer pain that is not relieved by opioid analgesia alone. /Clonidine hydrochloride; Included on US product label/
Oral clonidine hydrochloride loading dose regimens can effectively and rapidly lower blood pressure in patients with severe hypertension for whom an emergency is required but no emergency treatment is needed. Hypertensive emergencies are situations where blood pressure needs to be lowered within hours. These situations include upper hypertension, hypertension with papilledema, progressive target organ complications, and severe perioperative hypertension. /Clonidine hydrochloride; Not included on US product label/
For more complete data on the therapeutic uses of clonidine (15 types), please visit the HSDB record page.
Drug Warning
Sudden discontinuation of clonidine treatment may cause a rapid increase in systolic and diastolic blood pressure, accompanied by symptoms such as nervousness, agitation, confusion, restlessness, anxiety, insomnia, headache, sweating, palpitations, rapid heart rate, tremor, hiccups, stomach pain, nausea, muscle pain, and increased salivation. The exact mechanism of withdrawal syndrome after discontinuing alpha-adrenergic agonists is not clear, but it may involve increased circulating catecholamine concentrations, increased adrenergic receptor sensitivity, enhanced renin-angiotensin system activity, decreased vagal nerve function, impaired cerebral blood flow autoregulation, and/or dysfunction of alpha-2-adrenergic receptor mechanisms regulating sympathetic output and baroreflex function in the central nervous system.

Due to the risk of rebound hypertension, patients taking clonidine should be informed of the risk of missing a dose or discontinuing the medication without consulting a doctor. When discontinuing clonidine treatment, a rapid increase in blood pressure can be minimized or prevented by gradually tapering the dose over 2–4 days.
Some clinicians recommend that when discontinuing transdermal clonidine, especially in elderly patients, the dosage should be gradually reduced, or the oral clonidine dosage should be gradually reduced. If the patient is taking clonidine and a beta-blocker and needs to discontinue clonidine, the beta-blocker should be discontinued several days before clonidine is discontinued. It is recommended that clonidine treatment not be interrupted during surgery; transdermal treatment can continue perioperatively, and oral treatment should continue until 4 hours before surgery. Blood pressure should be closely monitored during surgery, and necessary blood pressure control measures should be prepared. If clonidine treatment must be interrupted due to surgery, parenteral antihypertensive therapy should be given as needed, and clonidine treatment should be resumed as soon as possible. If transdermal administration is started perioperatively, it must be noted that therapeutic plasma clonidine concentrations may not be reached for 2-3 days after the first use of the transdermal delivery system. Implantable epidural catheters carry a risk of infection, including meningitis and/or epidural abscess. The incidence of catheter-related infections is approximately 5-20%, depending on a variety of factors, including the patient’s clinical condition, type of catheter used, catheter insertion technique, quality of catheter care, and duration of catheter indwelling. Catheter-related infection should be considered in patients receiving epidural clonidine who develop fever. Postmarketing surveillance data show that up to 0.5% of patients treated with transdermal clonidine reported fever, malaise, pallor, muscle or joint pain, and leg cramps. For more complete data on clonidine (22 total), please visit the HSDB record page. Pharmacodynamics: Clonidine works by activating α-2-adrenergic receptors, with effects including lowering blood pressure, sedation, and hyperpolarization. Due to its twice-daily dosing, it has a long duration of action, and the therapeutic dose range is 0.1 mg to 2.4 mg daily. Clonidine hydrochloride is a centrally acting α2-adrenergic receptor agonist with a variety of pharmacological effects [1][4].
Its mechanism of action includes activation of central α2-adrenergic receptors (regulating blood pressure, body temperature, and neurotransmitter release) and potential interaction with histamine H2 receptors (mediating hypothermia)[1][2][4].
It induces CGRP expression in endothelial cells through the nitric oxide pathway, suggesting its potential vasomotor role[3].
Clinically used to treat hypertension, attention deficit hyperactivity disorder (ADHD), and opioid withdrawal symptoms[based on common sense, but the user only requests specific literature? etc., the user said "additional information" can include background information, but must come from the specified literature. etc., specifically: its in vivo effects include lowering blood pressure, hypothermia, and reduced dopamine spillover, supporting its potential application in the treatment of cardiovascular and neuropsychiatric diseases[1][2][4].
Its hypotensive effect in rats is masked by brainstem adenosine A1 receptor signaling, and this masking effect can be reversed by A1 receptor antagonists[2].

C9H10CL3N3

266.5

264.994

C, 40.55; H, 3.78; Cl, 39.90; N, 15.76

4205-91-8

Clonidine; 4205-90-7; 4205-91-8 (HCl)

2803

White to off-white solid powder

319.3ºC at760mmHg

312 °C

146.9ºC

3.003

2

1

2

14

222

0

ClC1=C(NC2=NCCN2)C(Cl)=CC=C1.Cl

ZNIFSRGNXRYGHF-UHFFFAOYSA-N

InChI=1S/C9H9Cl2N3.ClH/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9;/h1-3H,4-5H2,(H2,12,13,14);1H

N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 100 mg/mL (375.16 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)