Clonidin

Clonidin · CLONIDINE BASE · Kapvay · 734571A · m-5041t · Arkamin · Nexiclon · ST-155-BS

Identifikatoren & physikalische Daten

CAS No.	4205-90-7
Summenformel	C9H9Cl2N3
Durchschnittliche Molmasse	230,09 g/mol
Monoisotopische Masse	229,01735265 g/mol
SMILES	Clc1cccc(Cl)c1NC1=NCCN1
InChIKey	GJSURZIOUXUGAL-UHFFFAOYSA-N
PubChem CID	2803
ChEMBL	CHEMBL134
ChEBI	CHEBI:3757
EC No.	224-119-4
DTXSID	DTXSID6022846
Lokaler Name	Clonidin

Chemische & physikalische Eigenschaften

XLogP	1,6
Polarare Oberfläche (TPSA)	36,4
H-Brücken-Donoren	2
H-Brücken-Akzeptoren	1
Frei drehbare Bindungen	2
Schwere Atome	14
Formalladung	0
Komplexität	222
Stoffklassen	Pharmaceutical
Arzneimittel	Pharmaceuticals -> AntihypertensivesPharmaceuticals -> Listed in ZINC15
LogP (Verteilungskoeffizient)	log Kow = 1.572.7
Color/Form	Crystals
Löslichkeit	Insoluble in water4.80e-01 g/LDMSO:100.0(Max Conc. mg/mL)434.61(Max Conc. mM)
Human Drugs	Breast FeedingLactationMilk, HumanAntihypertensive AgentsAdrenergic alpha-2 Receptor AgonistsFDA approved drugs -> Active ingredientPharmaceuticals
Decomposition	When heated to decomposition it emits toxic fumes of nitroxides and /hydrogen chloride/. /Clonidine hydrochloride/
Schmelzpunkt	130 °CMP: 305 °C. Soluble in aboslute ethanol. One gram is soluble in 6 mLs water (60 °C)about 13 mLs water (20 °C)about 5.8 mLs methanolabout 25 mLs ethanolabout 5000 mLs chloroform. UV max (water): 213, 271, 302 nm (epsilon 8290.327, 713.074, 339.876) /Clonidine hydrochloride/141-142℃
Physical Description	Solid
Stability/Shelf Life	STABLE IN LIGHT, AIR, & HEAT /HCL/
Dissociation Constants	8.05 (at 25 °C)pKa = 8.05Odorless, bitter tastingpKa 8.2does not exhibit polymorphism. White to off-white crystalline powder. 1 g in about 13 mL water at 20 °C1 g in about 25 mL alcohol1 g in about 5000 mL chloroform /Clonidine hydrochloride/
Collision Cross Section	146.5 Å² [M+H]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID8044670]144 Å² [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)]142.2 Å² [M+H]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]
Siedepunkt	369.21°C (rough estimate)
Dichte	1.3946 (rough estimate)
Brechungsindex	1.6300 (estimate)
Flammpunkt	9℃
Lagerbedingungen	-20°C
Aggregatzustand	Solid
pKa (Säurekonstante)	8.10±0.50(Predicted)
Farbe	White to Off-White
Henry-Konstante	6.6×105 mol/(m3Pa) at 25℃, HSDB (2015)
Hauptanwendungen	pharmaceutical (small molecule)
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)
InChIKey	GJSURZIOUXUGAL-UHFFFAOYSA-N
SMILES	Clc1c(c(ccc1)Cl)NC2=NCCN2
CAS Datenbank	4205-90-7(CAS DataBase Reference)
EPA chemische Informationen	1H-Imidazol-2-amine, N-(2,6-dichlorophenyl)-4,5-dihydro- (4205-90-7)

Sicherheit & Vorschriften

GHS-Einstufung	DangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]P260, P262, P264, P270, P271, P280, P284, P301+P316, P302+P352, P304+P340, P316, P320, P321, P330, P361+P364, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 95 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Weitere Sicherheitsinformationen	IMAP assessments - 1H-Imidazol-2-amine, N-(2,6-dichlorophenyl)-4,5-dihydro-: Environment tier I assessment
FDA-Anforderungen	The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including clonidine, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including clonidine hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Clonidine hydrochloride/
Hazard Classes and Categories	Acute Tox. 3 (100%)
Lagerbedingungen	The commercially available transdermal system of clonidine should be stored at a temperature less than 30 °C. Clonidine hydrochloride tablets should be stored in tight, light-resistant containers at a controlled room temperature of 25 °C, but may be exposed to temperatures ranging from 15-30 °C. ... Commercially available clonidine hydrochloride injection should be stored at controlled room temperature of 25 °C, but may be exposed to temperatures ranging from 15-30 °C.
Entsorgungsverfahren	SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
Treatment	There is no specific antidote for clonidine overdosage. Clonidine overdosage may result in the rapid development of CNS depressiontherefore, induction of vomiting with ipecac syrup is not recommended. Gastric lavage may be indicated following recent and/or large ingestions. Administration of activated charcoal and/or a cathartic may be beneficial. Supportive care may include atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension and vasodilators for hypertension. Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression, hypotension and/or comablood pressure should be monitored since the administration of naloxone has occasionally resulted in paradoxical hypertension. Tolazoline administration has yielded inconsistent results and is not recommended as first-line therapy. (L1712)
Wechselwirkungen	Potential additive effects (eg, hypotension, bradycardia). If carvedilol is used concomitantly with clonidine, caution should be exercised, particularly when discontinuing therapycarvedilol 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 discontinuedBecause 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.
Hepatotoxicity	Serum aminotransferase elevations during clonidine therapy are uncommon and rates of such elevations have not been reported in the large clinical trials, demonstrating its efficacy in hypertension. Despite many decades of use, clonidine has not been implicated in instances of clinically apparent acute liver injury.
Umweltverhalten	TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 52(SRC), determined from a log Kow of 1.59(2) and a regression-derived equation(3), indicates that clonidine is expected to have high mobility in soil(SRC). The pKa of clonidine is 8.05(4), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of Clonidine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.5X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Clonidine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.9X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(5). Biodegradation data in soil were not available(SRC, 2011).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 52(SRC), determined from a log Kow of 1.59(2) and a regression-derived equation(3), indicates that clonidine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 1.5X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 5(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2011).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), clonidine, which has an estimated vapor pressure of 1.9X10-5 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase clonidine is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC)the half-life for this reaction in air is estimated to be 1 hour(SRC), calculated from its rate constant of 1.4X10-10 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase clonidine may be removed from the air by wet or dry deposition(SRC). Clonidine does not contain chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).
Unerwünschte Wirkungen	Like other medications, clonidine has the potential for short-term and long-term adverse effects. According to FDA reports, commonly observed reactions include the following:
Expositionspfade	Well absorbed following oral administration. Bioavailability following chronic administration is approximately 65%.
Milk Concentrations	Animal studies indicate that clonidine is widely distributed into body tissuestissue 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 dosethe drug was not detected in the plasma of the infant 1 hour after nursing.
Toxizitätsübersicht	Signs and Symptoms of OverdoseClonidine 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.
Signs and Symptoms	Symptoms of overdose include constriction of pupils of the eye, drowsiness, high blood pressure followed by a drop in pressure, irritability, low body temperature, slowed breathing, slowed heartbeat, slowed reflexes, and weakness.
Soil Adsorption/Mobility	The Koc of clonidine is estimated as 52(SRC), using a log Kow of 1.59(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that clonidine is expected to have high mobility in soil. The pKa of clonidine is 8.05(1), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).
Human Toxicity Excerpts	/SIGNS AND SYMPTOMS/ The initial effect is usually mental status depression, which occurs within an hour of ingestion. Life-threatening signs of clonidine poisoning include apnea, coma, bradycardia, and hypotension. It also cause miosis and hypothermia. Cardiovascular effects usually follow central nervous system effects./SIGNS AND SYMPTOMS/ Hypotension is usually mild but may be more severe after large ingestion. The more direct and dangerous effects is hypoventilation and apnea from central respiratory failure. Coma and apnea are common effects after a large overdose. The mental status change is curious in that tactile stimulation has been noted to awaken the patient. For example, testing for a Babinski reflex may transiently awaken a formerly unresponsive patient./SIGNS AND SYMPTOMS/ Children may be more likely to experience CNS depression associated with clonidine overdosage. In children, signs of toxicity have occurred with oral clonidine doses as low as 0.1 mg. Rare cases of clonidine toxicity (many involving children) associated with accidental or deliberate mouthing or ingestion of clonidine transdermal systems have been reported./SIGNS AND SYMPTOMS/ Signs and symptoms of overdosage of clonidine include hypotension (which may be profound), transient hypertension, weakness, vomiting, irritability, diminished or absent reflexes, lethargy, somnolence, drowsiness, deep sedation, irritability, skin pallor, hypothermia, decreased or irregular heart rate, dryness of the mouth, constricted pupils with poor reaction to light, respiratory depression, and hypoventilation. Large overdoses may result in reversible cardiac conduction defects or dysrhythmias, apnea, coma, and seizures. Signs and symptoms of clonidine overdosage usually occur within 30-120 minutes after ingestion.For more Human Toxicity Excerpts (Complete) data for CLONIDINE (15 total), please visit the HSDB record page.
Artificial Pollution Sources	Clonidine's production and use as medication(1) may result in its release to the environment through various waste streams(SRC).
Wassergefährdungsklasse (WGK)	1
UN-Transportnummer	UN1230 - class 3 - PG 2 - Methanol, solution
Zollcode	2933290000
R-Sätze (R)	11-23/24/25-39/23/24/25
Toxizität	LD50 oral in rat: 67300ug/kg
Gefahrensymbole	F,T
Sicherheitshinweise (S)	16-36/37-45
Lagerklasse	6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Gefahrstoffdaten	4205-90-7(Hazardous Substances Data)
Gefahrenklasse	Acute Tox. 3 Oral

Anwendungen & Verwendung

Verwenden

Clonidine may be useful in the treatment of acute opioid withdrawal. Epidural clonidine 1–2μgkg –1 increases the duration and potency of analgesia provided by epidural opioid or local anaesthetic drugs.