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Clonidine Hydrochloride

HCID 20179
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Basic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes
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Basic information

CAS
4205-91-8
Standard SMILES
Cl.Clc1cccc(Cl)c1NC1=NCCN1
InChIKey
ZNIFSRGNXRYGHF-UHFFFAOYSA-N
Molecular formula
C9H10Cl3N3
Average molar mass
266.6 g/mol
Monoisotopic mass
264.99403036

Overview

Clonidine hydrochloride is a dichlorobenzene.

Names & identifiers

Preferred name
Clonidine Hydrochloride
IUPAC
N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine;hydrochloride
English name
Clonidine hydrochloride
Molecular formula
C9H10Cl3N3
Molecular weight
266.55

Names & synonyms

CLONIDINE HYDROCHLORIDE4205-91-8Clonidine HClDuraclonKapvayST-155JenlogaDTXSID8044670Onyda XRNSC-756699W76I6XXF062-((2,6-Dichlorophenyl)imino)imidazolidine monohydrochloride
Show more names
dcai2-(2,6-DICHLOROANILINO)-2-IMIDAZOLINE HYDROCHLORIDEDIXARIThemitonNeuclonatensinacapresinclofelinhaemiton
Benzenamine, 2,6-dichloro-N-2-imidazolidinylidene-, monohydrochlorideDTXCID60246702-[(2,6-Dichlorophenyl)imino]imidazolidine monohydrochlorideClonidine HCICatapres tts 1Catapres tts 2Catapres tts 3Catapres p.l.

Database identifiers

CAS
4205-91-8
PubChem CID
20179
DTXSID
DTXSID8044670
ChEMBL
CHEMBL1705
ChEBI
CHEBI:3758
UNII
W76I6XXF06
EC Number
224-121-5

Properties

Computed structural propertiesFilling in

Topological polar surface area
36.4 Ų
Hydrogen bond donors
3
Hydrogen bond acceptors
1
Rotatable bonds
2
Heavy atoms
15
Formal charge
0
Complexity
222

Experimental & physicochemical properties

Human Drugs · 3 items

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Collision Cross Section143.3 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Physicochemical properties

Melting point
312 °C · 312 °C
storage temp.
2 · 2-8°C
solubility
2 O: · H2O: 50 mg/mL, clear, colorless
form
solid
color
white
PH
pH(50g/l, 25℃) : 3.5~6.0
Water Solubility
Soluble in water (50 mg/ml), DMSO (75 mM), methanol, chloroform (slightly), and dehydrated alcohol.
Merck
14 · 14,2390
BRN
4163525 · 4163525
BCS Class
1 · 1 (LogP), 3 (CLogP)

Safety & regulation

Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.

GHS classification

GHS Classification · 4 items

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P260, P264, P270, P271, P284, P301+P316, P304+P340, P316, P320, P321, P330, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 49 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard information

Regulatory Information1H-Imidazol-2-amine, N-(2,6-dichlorophenyl)-4,5-dihydro-, monohydrochloride: Does not have an individual approval but may be used under an appropriate group standard
Other Safety InformationIMAP assessments - Benzenamine, 2,6-dichloro-N-2-imidazolidinylidene-, monohydrochloride: Human health tier I assessment
Hazard Classes and CategoriesAcute Tox. 3 (100%)

Toxicology

Treatment · 1 item

There is no specific antidote for clonidine overdosage. Clonidine overdosage may result in the rapid development of CNS depression; therefore, 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 coma; blood 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)

Chemistry & industry

Pharmacology

Metabolism/Metabolites · 1 item

Hepatic. Metabolized via minor pathways. The major metabolite, <i>p</i>-hydroxyclonidine, is present in concentrations less than 10% of those of unchanged clonidine in urine. Four metabolites have been detected, but only <i>p</i>-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 <i>p</i>-hydroxyclonidine.

FDA Pharmacological Classification · 4 items

CLONIDINE HCI

Central alpha-2 Adrenergic Agonist [EPC]; Adrenergic alpha2-Agonists [MoA]

CLONIDINE HYDROCHLORIDE

Adrenergic alpha2-Agonists [MoA]; Central alpha-2 Adrenergic Agonist [EPC]

MeSH Pharmacological Classification · 4 items

Compounds capable of relieving pain without the loss of CONSCIOUSNESS.

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

Drugs that inhibit the actions of the sympathetic nervous system by any mechanism. The most common of these are the ADRENERGIC ANTAGONISTS and drugs that deplete norepinephrine or reduce the release of transmitters from adrenergic postganglionic terminals (see ADRENERGIC AGENTS). Drugs that act in the central nervous system to reduce sympathetic activity (e.g., centrally acting alpha-2 adrenergic agonists, see ADRENERGIC ALPHA-AGONISTS) are included here.

Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.

Uses & manufacturing

Uses · 1 item

May be used as an adjunct in the treatment of hypertension, as an epidural infusion as an adjunct treatment in the management of severe cancer pain that is not relieved by opiate analgesics alone, for differential diagnosis of pheochromocytoma in hypertensive patients, prophylaxis of vascular migraine headaches, treatment of severe dysmenorrhea, management of vasomotor symptoms associated with menopause, rapid detoxification in the management of opiate withdrawal, treatment of alcohol withdrawal used in conjunction with benzodiazepines, management of nicotine dependence, topical use to reduce intraocular pressure in the treatment of open-angle and secondary glaucoma and hemorrhagic glaucoma associated with hypertension, and in the treatment of attention-deficit hyperactivity disorder (ADHD).

Related reactions

2 records
New reaction record
HRID 716609 reaction equation
HRID 716609As reactantuspto-grants-2015_11
HRID 1527648 reaction equation
HRID 1527648As reactantuspto-grants-2015_07

Compound notes

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On this pageBasic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes
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Stability
Hygroscopic
Major Application
pharmaceutical (small molecule)
InChI
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
InChIKey
GLEWMLFXCSBZLK-UHFFFAOYSA-N
SMILES
C1(=C(Cl)C=CC=C1Cl)NC1=NCCN1.Cl
CAS DataBase Reference
4205 · 4205-91-8(CAS DataBase Reference)
NCI Dictionary of Cancer Terms
clonidine hydrochloride
FDA UNII
76 I6XXF06 · W76I6XXF06
NCI Drug Dictionary
clonidine hydrochloride
EPA Substance Registry System
1 H-Imidazol-2-amine, · 1H-Imidazol-2-amine, N-(2,6-dichlorophenyl)-4,5-dihydro-, hydrochloride (1:1) (4205-91-8)
UNSPSC Code
41116107 · 41116107
NACRES
77 · NA.77
Protein binding
30 · 30-40%
Excreted unchanged in urine
40 · 40-60%
Volume of distribution
3 · 3-6(L/kg)
Biological half-life
10 · 10-20 / 41
Symbol(GHS)
6 · GHS06
Signal word
Danger
Hazard statements
301 · H301-H330
Precautionary statements
260 · P260-P301+P330+P331+P310-P304+P340+P310-P403+P233
Hazard Codes
T+
Risk Statements
25 · 25-26
Safety Statements
22 · 22-26-28-36/37/39-45
RIDADR
2811 · UN 2811 6.1/PG 1
WGK Germany
3 · 3
RTECS
2490000 · NJ2490000
F
10 · 10
HazardClass
6.1 · 6.1(b)
PackingGroup
III
HS Code
2933290000 · 2933290000
Storage Class
6.1 A · 6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials
Hazard Classifications
1 InhalationAcute · Acute Tox. 1 InhalationAcute Tox. 3 Oral
Toxicity
50 in · LD50 in mice, rats (mg/kg): 328, 270 orally; 18, 29 i.v. (Walland)
Excepted Quantities
Max Inner Pack (1g or 1ml) and Max Outer Pack (300g or 300ml)
Exposure RoutesWell absorbed following oral administration. Bioavailability following chronic administration is approximately 65%.
Toxicity Summary · 1 item

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.

Signs and SymptomsSymptoms 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.
Carcinogen ClassificationNo indication of carcinogenicity to humans (not listed by IARC).
Drug Induced Liver Injury · 6 items

Drug Induced Liver Injury Rank (DILIrank 2.0)

Clonidine hydrochloride

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
Toxicity DataLD50: 150 mg/kg (oral, rat) LD50: 30 mg/kg (oral, dog)

Safety data

F
10
wgk
3
rtecs
NJ2490000
ridadr
UN 2811 6.1/PG 1
hs_code
2933290000
Toxicity
LD50 in mice, rats (mg/kg): 328, 270 orally; 18, 29 i.v. (Walland)
risk_code
25-26
Signal word
Danger
Symbol(GHS)
GHS06
hazard_code
T+
safety_code
22-26-28-36/37/39-45
hazard_class
6.1(b)
Storage Class
6.1A - Combustible acute toxic Cat. 1 and 2very toxic hazardous materials
packing_group
III
Hazard statements
H301-H330
Excepted Quantities
Max Inner Pack (1g or 1ml) and Max Outer Pack (300g or 300ml)
Hazard Classifications
Acute Tox. 1 InhalationAcute Tox. 3 Oral
Precautionary statements
P260-P301+P330+P331+P310-P304+P340+P310-P403+P233
Applications · 5 items

UsesClonidine hydrochloride tablets are indicated in the treatment of hypertension. It has found new uses, including treatment of some types of neuropathic pain, opioid detoxification, sleep hyperhidrosis, anaesthetic use, and off-label, to counter the side effects of stimulant medications such as methylphenidate or amphetamine. It is becoming a more accepted treatment for insomnia, as well as for relief of menopausal symptoms. Clonidine(4205-91-8) is increasingly used in conjunction with stimulants to treat attention-deficit hyperactivity disorder (ADHD).

Uses`a2-adrenoceptor agonist, imidazoline receptor ligand, anti-hypertensive

UsesIn shaving soaps.

UsesLabelled Clonidine. α2-Adrenergic agonist. Antihypertensive; analgesic for neuropathic pain.

General DescriptionClonidine hydrochloride, 2-[(2,6-dichlorophenyl)imino]imidazolidine monohydrochloride(Catapres), was the first antihypertensive known to acton the CNS. It was synthesized in 1962 as a derivativeof the known -sympathomimetic drugs naphazoline andtolazoline, potential nasal vasoconstrictors, but instead itproved to be effective in the treatment of mild-to-severe hypertension.Clonidine hydrochloride acts by both peripheral andcentral mechanisms in the body to affect blood pressure. Itstimulates the peripheral -adrenergic receptors to producevasoconstriction, resulting in a brief period of hypertension.

Upstream & downstream products

Upstream raw materials

2,6-DichloroanilineIodomethaneHydrogenthiocyanateEthylenediamineEthanolDichlorphenamide bulk powderCLONIDINEHydrochloric acidWater

Additional notes

DefinitionChEBI: Clonidine hydrochloride is a dichlorobenzene.