α2-adrenergic receptor

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].

---

Neurons' ability to fire is inhibited by clonidine [5]. The dorsal raphe (DR) nucleus is a system of nuclei in the midline of the lower brainstem, which is considered one of the most important nuclei in the modulation of pain in the central nervous system. Central noradrenergic systems play an important role in the control of cardiovascular regulation and pain transmission. Clonidine, an alpha 2-adrenergic agonist is used extensively in anesthesia research. In this study, we evaluated the involvement of clonidine in the activity of DR nucleus and its possible role in pain modulation. Seventy-four neurons within the DR nucleus in the rat brainstem slice preparation were tested using extracellular recording techniques. Application of noradrenaline (NA), 50 mumol/L, induced firing activity in 68 neurons tested (92%). NA produced a regular long-lasting firing activity on the DR neurons. Fifty-six neurons (88%) previously excited by NA were inhibited by clonidine, 20 mumol/L. Clonidine suppressed the firing activity of neurons. The results indicate that the firing of DR neurons was under noradrenergic influence and was inhibited by clonidine, which in turn alters nociception by modifying the central serotonergic system [5].

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].

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].

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].

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).

---

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]

Absorption, Distribution and Excretion
Clonidine reaches maximum concentration in 60-90 minutes after oral administration. Race and fasting status do not influence pharmacokinetics of clonidine. A 100µg oral clonidine tablet reaches a Cmax of 400.72pg/mL with an AUC of 5606.78h\*pg/mL and a bioavailability of 55-87%.
Approximately 50% of a clonidine dose is excreted in the urine as the unchanged drug and 20% is eliminated in the feces.
The volume of distribution of clonidine has been reported as 1.7-2.5L/kg, 2.9L/kg, or 2.1±0.4L/kg depending on the source.
The clearance of clonidine is 1.9-4.3mL/min/kg.
Animal studies indicate that clonidine is widely distributed into body tissues; tissue concentrations of the drug are higher than plasma concentrations. The mean volume of distribution of clonidine is reported to be 2.1 L/kg. After oral administration, highest concentrations of the drug are found in the kidneys, liver, spleen, and GI tract. High concentrations of the drug also appear in the lacrimal and parotid glands. Clonidine is concentrated in the choroid of the eye and is also distributed into the heart, lungs, testes, adrenal glands, fat, and muscle. The lowest concentration occurs in the brain. Clonidine is distributed into CSF. Following epidural infusion, clonidine is rapidly and extensively distributed into CSF and readily partitions into the plasma via epidural veins. In vitro, clonidine is approximately 20-40% bound to plasma proteins, mainly albumin. Clonidine crosses the placenta1 and is distributed into milk. In one lactating woman who received approximately 0.04 mg of oral clonidine hydrochloride twice daily and 25 mg of oral dihydralazine 3 times daily, clonidine concentrations were 0.33 ng/mL in a plasma sample obtained 1 hour after a dose and 0.6 ng/mL in a milk sample obtained 2.5 hours after a dose; the drug was not detected in the plasma of the infant 1 hour after nursing.
...IN HEALTHY VOLUNTEERS... AFTER IV INFUSION OF 300 UG CLONIDINE IN 10 MINUTES, PLASMA LEVELS OF DRUG DECLINED BI-EXPONENTIALLY WITH RAPID AND SLOW HALF-LIFE VALUES OF 11 MINUTES AND 8.5 HOURS, RESPECTIVELY.
THE PHARMACOKINETICS OF CLONIDINE WERE INVESTIGATED IN HEALTHY VOLUNTEERS OVER A TIME MORE THAN 3 TIMES LONGER THAN PREVIOUSLY REPORTED. APPROXIMATELY 62% OF A GIVEN DOSE WAS EXCRETED UNCHANGED IN URINE, INDEPENDENT OF THE QUANTITY ADMINISTERED, THE DRUG FORMULATION, OR THE MODE OF ADMINISTRATION. SINCE THE PHARMACOKINETICS OF THE DRUG WERE AFFECTED BY ENTEROHEPATIC CIRCULATION, IT CANNOT BE DESCRIBED BY A CONVENTIONAL, OPEN 1 OR 2 COMPARTMENT MODEL. THE TIME COURSES OF THE PLASMA CLONIDINE CONCENTRATION AND ITS DRUG EFFECTS RAN ASYNCHRONOUSLY.
CLONIDINE KINETICS WERE STUDIED IN 21 PATIENTS WITH ESSENTIAL HYPERTENSION WHO RECEIVED 2 BOLUS IV INJECTIONS (0.78-3.36 MCG/KG) AND ONE SINGLE ORAL DOSE (1.7-2.3 MCG/KG) ON SEPARATE OCCASIONS; KINETICS WERE STUDIED IN SOME PATIENTS AFTER MULTIPLE THERAPEUTIC ORAL DOSES (1.1 OR 1.9 MCG/KG TWICE DAILY) DURING A DOSAGE INTERVAL AFTER 6-12 MONTHS MONOTHERAPY WITH CLONIDINE. WITH INCREASING IV DOSES, THE RATE CONSTANTS DECREASED AND THE PLASMA CLEARANCE WAS REDUCED BY 74% (9.94-2.61 ML/MIN/KG) INDICATING DOSE-DEPENDENT KINETICS. THE VOLUME OF DISTRIBUTION DID NOT CHANGE WITH DOSE IN CONTRAST TO THE VOLUME OF THE PLASMA COMPARTMENT WHICH WAS INCREASED AT THE HIGHEST DOSES. THE SINGLE ORAL DOSE KINETICS AGREED WITH THE IV KINETICS AT COMPARABLE DOSE. THE BIOAVAILABILITY WAS 90%. DURING MULTIPLE ORAL DOSING THE ELIMINATION RATE CONSTANTS DECREASED COMPARED TO THE SINGLE DOSE. THE PLASMA CLEARANCE INCREASED (7.18 ML/MIN/KG) COMPARED TO THE CORRESPONDING SINGLE DOSE (4.17 ML/MIN/KG). THE LATTER CHANGE WAS PROBABLY CAUSED BY THE DECREASE IN BIOAVAILABILITY TO ABOUT 65%. IT WAS DETERMINED THAT THE PHARMACODYNAMIC PROPERTIES OF THE DRUG COULD EXPLAIN THE CHANGES IN PHARMACOKINETICS WITH INCREASED DOSE AND DURING MULTIPLE DOSES.
For more Absorption, Distribution and Excretion (Complete) data for CLONIDINE (8 total), please visit the HSDB record page.

---

Metabolism / Metabolites
The metabolism of clonidine is poorly understood. The main reaction in clonidine metabolism is the 4-hydroxylation of clonidine by CYP2D6, CYP1A2, CYP3A4, CYP1A1, and CYP3A5. Clonidine is <50% metabolized in the liver to inactive metabolites.
Clonidine hydrochloride is metabolized in the liver. In humans, 4 metabolites have been detected but only one, the inactive p-hydroxyclonidine, has been identified.
...Seventeen cDNA-expressed P450 enzymes, in addition to pooled human liver microsomes, were evaluated for clonidine 4-hydroxylation activity in vitro. Five P450 enzymes-CYP2D6, 1A2, 3A4, 1A1, and 3A5-catalyzed measurable formation of 4-hydroxyclonidine. Selective inhibition studies in human liver microsomes confirmed that these isoforms are jointly responsible for 4-hydroxylation of clonidine in vitro, and CYP2D6 accounted for approximately two-thirds of the activity. The major role of CYP2D6 in clonidine metabolism might explain the increase in its nonrenal clearance during pregnancy.
CLONIDINE SHOWS SPECIES DIFFERENCES IN THE EXTENT OF BIOTRANSFORMATION. THE FATE OF (14)C-CLONIDINE IN THE DOG HAS BEEN REPORTED AND SIX COMPONENTS WERE ISOLATED AND IDENTIFIED. UNCHANGED CLONIDINE AND ITS P-HYDROXYLATED DERIVATIVE WERE DETECTED. DICHLOROPHENYLGUANIDINE, WHICH HAS PREVIOUSLY BEEN REPORTED AS A METABOLITE IN DOGS, WAS ALSO IDENTIFIED. THREE METABOLITES NOT PREVIOUSLY DESCRIBED WERE ALSO ISOLATED FROM DOG URINE. THE MAJOR METABOLIC ROUTES FOR CLONIDINE ARE PHENYL RING HYDROXYLATION AND SPLITTING OF THE IMIDAZOLIDINE RING. COMPARATIVE STUDIES SHOWED THAT THE METABOLISM OF CLONIDINE IS RATHER SIMILAR IN RAT, DOG, AND MAN, BUT MAN EXCRETED MOST UNCHANGED DRUG AND DOG SHOWED THE MOST EXTENSIVE METABOLISM.
Hepatic. Metabolized via minor pathways. The major metabolite, p-hydroxyclonidine, is present in concentrations less than 10% of those of unchanged clonidine in urine. Four metabolites have been detected, but only p-hydroxyclonidine has been identified.
Half Life: 6-20 hours; 40-60% is excreted in urine unchanged, 20% is excreted in feces. Less than 10% is excreted by p-hydroxyclonidine.

---

Biological Half-Life
The elimination half life after epidural administration is 30 minutes but otherwise can range from 6-23h.
The elimination half-life of the drug ranges from 6 to 24 hours, with a mean of about 12 hours.
THE PHARMACOKINETICS OF CLONIDINE WERE INVESTIGATED IN HEALTHY VOLUNTEERS OVER A TIME MORE THAN 3 TIMES LONGER THAN PREVIOUSLY REPORTED. THE COMPLETE BIOAVAILABILITY OF CLONIDINE AND ITS ELIMINATION T/2 (20 TO 25.5 HOURS) REMAINED CONSTANT AFTER SINGLE AND MULTIPLE DOSES.
The plasma half-life of clonidine is 6-20 hours in patients with normal renal function. The half-life in patients with impaired renal function has been reported to range from 18-41 hours. The elimination half-life of the drug may be dose dependent, increasing with increasing dose.

Toxicity Summary
Clonidine acts as an agonist at presynaptic alpha(2)-receptors in the nucleus tractus solitarius of the medulla oblongata. Stimulation of these receptors results in the supression of efferent sympathetic pathways and the subsequent decrease in blood pressure and vascular tone in the heart, kidneys, and peripheral vasculature. Clonidine is also a partial agonist at presynaptic alpha(2)-adrenergic receptors of peripheral nerves in vascular smooth muscle.

---

Toxicity Data
LD50: 150 mg/kg (oral, rat)
LD50: 30 mg/kg (oral, dog)

---

Interactions
Potential additive effects (eg, hypotension, bradycardia). If carvedilol is used concomitantly with clonidine, caution should be exercised, particularly when discontinuing therapy; carvedilol generally should be discontinued first, and clonidine continued for several days thereafter with gradual downward dosage titration.
Epidural clonidine may prolong the duration of the pharmacologic effects, including both sensory and motor blockade, of epidural local anesthetics.
Because beta-adrenergic blocking agents may exacerbate rebound hypertension that may occur following discontinuance of clonidine therapy, beta-adrenergic blocking agents should be discontinued several days before gradual withdrawal of clonidine when clonidine therapy is to be discontinued in patients receiving a beta-adrenergic blocking agent and clonidine concurrently. If clonidine therapy is to be replaced by a beta-adrenergic blocking agent, administration of the beta-adrenergic blocking agent should be delayed for several days after clonidine therapy has been discontinued
Because clonidine may produce bradycardia and atrioventricular (AV) block, the possibility of additive effects should be considered if it is given concomitantly with other drugs that affect sinus node function or AV nodal conduction (e.g., guanethidine), beta-adrenergic blocking agents (e.g., propranolol), calcium-channel blocking agents, or cardiac glycosides.
For more Interactions (Complete) data for CLONIDINE (15 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LD50 Rat oral 126 mg/kg /Clonidine hydrochloride/
LD50 Rat ip 100 mg/kg /Clonidine hydrochloride/
LD50 Rat iv 29 mg/kg /Clonidine hydrochloride/
LD50 Rat sc 77 mg/kg /Clonidine hydrochloride/
For more Non-Human Toxicity Values (Complete) data for CLONIDINE (9 total), please visit the HSDB record page.

[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.

[5]. The effect of clonidine on the activity of neurons in the rat dorsal raphe nucleus in vitro. Anesth Analg. 1994 Aug;79(2):257-60.

Therapeutic Uses
Adrenergic alpha-Agonists; Antihypertensive Agents; Sympatholytics; Analgesics
Clonidine hydrochloride and transdermal clonidine are used alone or in combination with other classes of antihypertensive agents in the management of hypertension. /Included in US product labeling/
Clonidine hydrochloride administered by epidural infusion is used as adjunctive therapy in combination with opiates in the management of severe cancer pain that is not relieved by opiate analgesics alone. /Clonidine hydrochloride; Included in US product labeling/
Oral loading-dose regimens of clonidine hydrochloride have been effective in rapidly reducing blood pressure in patients with severe hypertension in whom reduction of blood pressure was considered urgent, but not requiring emergency treatment. Hypertensive urgencies are those situations in which it is desirable to reduce blood pressure within a few hours. Such situations include the upper levels of severe hypertension, hypertension with optic disk edema, progressive target organ complications, and severe perioperative hypertension. /Clonidine hydrochloride; NOT included in US product labeling/
For more Therapeutic Uses (Complete) data for CLONIDINE (15 total), please visit the HSDB record page.

---

Drug Warnings
Abrupt withdrawal of clonidine therapy may result in a rapid increase of systolic and diastolic blood pressures with associated symptoms such as nervousness, agitation, confusion, restlessness, anxiety, insomnia, headache, sweating, palpitation, increased heart rate, tremor, hiccups, stomach pains, nausea, muscle pains, and increased salivation. The exact mechanism(s) of the withdrawal syndrome following discontinuance of alpha-adrenergic agonists has not been determined but may involve increased concentrations of circulating catecholamines, increased sensitivity of adrenergic receptors, enhanced renin-angiotensin system activity, decreased vagal function, failure of autoregulation of cerebral blood flow, and/or failure of central alpha2-adrenergic receptor mechanisms that regulate sympathetic outflow from the CNS and modulate baroreflex function.
Because of the risk of rebound hypertension, patients receiving clonidine preparations should be warned of the danger of missing doses or stopping the drug without consulting their physician. When discontinuing clonidine therapy, a rapid rise in blood pressure may be minimized or prevented by tapered withdrawal of the drug over 2-4 days. Tapered withdrawal of transdermal clonidine or initiation of a tapered regimen of oral clonidine also is recommended by some clinicians when the transdermal dosage form is discontinued, particularly in geriatric patients. If clonidine therapy is to be discontinued in patients receiving clonidine and a beta-adrenergic blocking agent concomitantly, the beta-adrenergic blocker should be discontinued several days before clonidine therapy is discontinued. It is recommended that clonidine therapy not be interrupted for surgery; transdermal therapy can be continued throughout the perioperative period and oral therapy should be continued to within 4 hours before surgery. Blood pressure should be carefully monitored during surgery and additional measures to control blood pressure should be available if necessary. If clonidine therapy must be interrupted for surgery, parenteral hypotensive therapy should be administered as necessary, and clonidine therapy should be resumed as soon as possible. If transdermal therapy is initiated during the perioperative period, it must be kept in mind that therapeutic plasma clonidine concentrations are not achieved until 2-3 days after initial application of the transdermal system.
Implantable epidural catheters are associated with a risk of infection, including meningitis and/or epidural abscess. The incidence of catheter-related infections is about 5-20%, and depends on several factors, including the clinical status of the patient, type of catheter used, catheter placement technique, quality of catheter care, and duration of catheter placement. The possibility of catheter-related infection should be considered in patients receiving epidural clonidine who develop a fever.
Fever, malaise, pallor, muscle or joint pain, and leg cramps have been reported in up to 0.5% of patients during postmarketing experience with transdermal clonidine.
For more Drug Warnings (Complete) data for CLONIDINE (22 total), please visit the HSDB record page.

---

Pharmacodynamics
Clonidine functions through agonism of alpha-2 adrenoceptors which have effects such as lowering blood pressure, sedation, and hyperpolarization of nerves. It has a long duration of action as it is given twice daily and the therapeutic window is between 0.1mg and 2.4mg daily.

C9H9CL2N3

230.094

229.017

C, 46.98; H, 3.94; Cl, 30.82; N, 18.26

4205-90-7

Clonidine hydrochloride;4205-91-8;Clonidine-d4 hydrochloride;67151-02-4

2803

White to off-white solid powder

1.5±0.1 g/cm3

319.3±52.0 °C at 760 mmHg

141-142℃

146.9±30.7 °C

0.0±0.7 mmHg at 25°C

1.671

1.41

2

1

2

14

222

0

GJSURZIOUXUGAL-UHFFFAOYSA-N

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

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

clonidine; 4205-90-7; Clonidin; Chlornidinum; N-(2,6-Dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine; Catapres-TTS; Adesipress; Catapres;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

DMSO : ~100 mg/mL (~434.61 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (10.87 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (10.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (10.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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