U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C62H88N13O14P.C2H3O2.Co
Molecular Weight 1388.3918
Optical Activity UNSPECIFIED
Defined Stereocenters 13 / 14
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of HYDROXOCOBALAMIN ACETATE

SMILES

[Co+3].CC([O-])=O.C[C@H](CNC(=O)CC[C@]1(C)[C@@H](CC(N)=O)C2[N-]C1=C(C)C3=NC(=CC4=NC(=C(C)C5=N[C@]2(C)[C@@](C)(CC(N)=O)[C@@H]5CCC(N)=O)[C@@](C)(CC(N)=O)[C@@H]4CCC(N)=O)C(C)(C)[C@@H]3CCC(N)=O)OP([O-])(=O)O[C@@H]6[C@@H](CO)O[C@@H]([C@@H]6O)N7C=NC8=C7C=C(C)C(C)=C8

InChI

InChIKey=KPFAAKYTRSSOQN-UVKKECPRSA-K
InChI=1S/C62H90N13O14P.C2H4O2.Co/c1-29-20-39-40(21-30(29)2)75(28-70-39)57-52(84)53(41(27-76)87-57)89-90(85,86)88-31(3)26-69-49(83)18-19-59(8)37(22-46(66)80)56-62(11)61(10,25-48(68)82)36(14-17-45(65)79)51(74-62)33(5)55-60(9,24-47(67)81)34(12-15-43(63)77)38(71-55)23-42-58(6,7)35(13-16-44(64)78)50(72-42)32(4)54(59)73-56;1-2(3)4;/h20-21,23,28,31,34-37,41,52-53,56-57,76,84H,12-19,22,24-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);1H3,(H,3,4);/q;;+3/p-3/t31-,34-,35-,36-,37+,41-,52-,53-,56?,57+,59-,60+,61+,62+;;/m1../s1

HIDE SMILES / InChI
Hydroxocobalamin (also hydroxycobalamin, OHCbl) is a natural form, or vitamer, of vitamin B12. It is a member of the cobalamin family of compounds. Hydroxocobalamin, the active ingredient in Cyanokit, is cobinamide dihydroxide dihydrogen phosphate (ester), mono (inner salt), 3’-ester with 5,6-dimethyl-1-α-D-ribofuranosyl-1H-benzimidazole. The drug substance is the hydroxylated active form of vitamin B12 and is a large molecule in which a trivalent cobalt ion is coordinated in four positions by a tetrapyrol (or corrin) ring. It is a hygroscopic, odorless, dark red, crystalline powder that is freely soluble in water and ethanol, and practically insoluble in acetone and diethyl ether. Cyanokit contains hydroxocobalamin, an antidote indicated for the treatment of known or suspected cyanide poisoning. Cyanide is an extremely toxic poison. In the absence of rapid and adequate treatment, exposure to a high dose of cyanide can result in death within minutes due to the inhibition of cytochrome oxidase resulting in arrest of cellular respiration. Specifically, cyanide binds rapidly with cytochrome a3, a component of the cytochrome c oxidase complex in mitochondria. Inhibition of cytochrome a3 prevents the cell from using oxygen and forces anaerobic metabolism, resulting in lactate production, cellular hypoxia and metabolic acidosis. In massive acute cyanide poisoning, the mechanism of toxicity may involve other enzyme systems as well. Signs and symptoms of acute systemic cyanide poisoning may develop rapidly within minutes, depending on the route and extent of cyanide exposure. The action of Cyanokit is based on its ability to bind cyanide ions. Each hydroxocobalamin molecule can bind one cyanide ion by substituting it for the hydroxo ligand linked to the trivalent cobalt ion, to form cyanocobalamin, which is then excreted in the urine.

CNS Activity

Curator's Comment: Acetic acid was shown to cross the blood brain barrier in rats.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
CYANOKIT

Approved Use

Cyanokit contains hydroxocobalamin, an antidote indicated for the treatment of known or suspected cyanide poisoning. (1.1) If clinical suspicion of cyanide poisoning is high, Cyanokit should be administered without delay. (1.2) The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222. (1.2) 1.1 Indication Cyanokit is indicated for the treatment of known or suspected cyanide poisoning. 1.2 Identifying Patients with Cyanide Poisoning Cyanide poisoning may result from inhalation, ingestion, or dermal exposure to various cyanide-containing compounds, including smoke from closed-space fires. Sources of cyanide poisoning include hydrogen cyanide and its salts, cyanogenic plants, aliphatic nitriles, and prolonged exposure to sodium nitroprusside. The presence and extent of cyanide poisoning are often initially unknown. There is no widely available, rapid, confirmatory cyanide blood test. Treatment decisions must be made on the basis of clinical history and signs and symptoms of cyanide intoxication. If clinical suspicion of cyanide poisoning is high, Cyanokit should be administered without delay. Table 1 Common Signs and Symptoms of Cyanide Poisoning Symptoms Signs Headache Altered Mental Status (e.g., confusion,disorientation) Confusion Seizures or Coma Dyspnea Mydriasis Chest tightness Tachypnea / Hyperpnea (early) Nausea Bradypnea / Apnea (late) Hypertension (early) / Hypotension (late) Cardiovascular collapse Vomiting Plasma lactate concentration ≥ 8 mmol/L In some settings, panic symptoms including tachypnea and vomiting may mimic early cyanide poisoning signs. The presence of altered mental status (e.g., confusion and disorientation) and/or mydriasis is suggestive of true cyanide poisoning although these signs can occur with other toxic exposures as well. The expert advice of a regional poison control center may be obtained by calling 1-800-222-1222. Smoke Inhalation Not all smoke inhalation victims will have cyanide poisoning and may present with burns, trauma, and exposure to other toxic substances making a diagnosis of cyanide poisoning particularly difficult. Prior to administration of Cyanokit, smoke-inhalation victims should be assessed for the following: Exposure to fire or smoke in an enclosed area Presence of soot around the mouth, nose or oropharynx Altered mental status Although hypotension is highly suggestive of cyanide poisoning, it is only present in a small percentage of cyanide-poisoned smoke inhalation victims. Also indicative of cyanide poisoning is a plasma lactate concentration ≥ 10 mmol/L (a value higher than that typically listed in the table of signs and symptoms of isolated cyanide poisoning because carbon monoxide associated with smoke inhalation also contributes to lactic acidemia). If cyanide poisoning is suspected, treatment should not be delayed to obtain a plasma lactate concentration. 1.3 Use with Other Cyanide Antidotes Caution should be exercised when administering other cyanide antidotes simultaneously with Cyanokit, as the safety of co-administration has not been established. If a decision is made to administer another cyanide antidote with Cyanokit, these drugs should not be administered concurrently in the same intravenous line. [see Dosage and Administration (2.3)

Launch Date

2006
Curative
VOSOL

Approved Use

For the treatment of superficial infections of the external auditory canal caused by organisms susceptible to the action of the antimicrobial.

Launch Date

1960
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4511.6 μM × h
5 g single, intravenous
dose: 5 g
route of administration: Intravenous
experiment type: SINGLE
co-administered:
HYDROXOCOBALAMIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
26.2 h
5 g single, intravenous
dose: 5 g
route of administration: Intravenous
experiment type: SINGLE
co-administered:
HYDROXOCOBALAMIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
20 mg 1 times / day multiple, intramuscular
Dose: 20 mg, 1 times / day
Route: intramuscular
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 13 years
n = 1
Health Status: unhealthy
Age Group: 13 years
Sex: M
Population Size: 1
Sources:
20 g single, intravenous
Highest studied dose
Dose: 20 g
Route: intravenous
Route: single
Dose: 20 g
Sources:
unhealthy, 26.9 years
n = 1
Health Status: unhealthy
Age Group: 26.9 years
Sex: M
Population Size: 1
Sources:
5 g single, intravenous
Overdose
Dose: 5 g
Route: intravenous
Route: single
Dose: 5 g
Sources:
unhealthy, 3 years
n = 1
Health Status: unhealthy
Condition: cyanide toxicity
Age Group: 3 years
Sex: F
Population Size: 1
Sources:
5 g single, intravenous
Dose: 5 g
Route: intravenous
Route: single
Dose: 5 g
Sources:
unhealthy, 62 years
n = 1
Health Status: unhealthy
Condition: Vasoplegic Syndrome
Age Group: 62 years
Sex: M
Population Size: 1
Sources:
2000 ug 2 times / day multiple, oral
Dose: 2000 ug, 2 times / day
Route: oral
Route: multiple
Dose: 2000 ug, 2 times / day
Sources:
unhealthy, adult
n = 8
Health Status: unhealthy
Condition: pernicious anaemia
Age Group: adult
Population Size: 8
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​Drug as victim

Drug as victim

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Subcellular localization of Rab17 by cryo-immunogold electron microscopy in epithelial cells grown on polycarbonate filters.
2001
Evaluation of copper availability to plants in copper-contaminated vineyard soils.
2001
Brain dystrophin-glycoprotein complex: persistent expression of beta-dystroglycan, impaired oligomerization of Dp71 and up-regulation of utrophins in animal models of muscular dystrophy.
2001
Fully automated on-line determination of olanzapine in serum for routine therapeutic drug monitoring.
2001 Feb
Exploring infection of wheat and carbohydrate metabolism in Mycosphaerella graminicola transformants with differentially regulated green fluorescent protein expression.
2001 Feb
In vivo (13)C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during.
2001 Feb
Analgesic and anti-inflammatory effects of Mangifera indica L. extract (Vimang).
2001 Feb
Metabolic shifts and myocyte hypertrophy in deflazacort treatment of mdx mouse cardiomyopathy.
2001 Feb
In silico predictions of Escherichia coli metabolic capabilities are consistent with experimental data.
2001 Feb
Structure of manganese diacetate tetrahydrate and low-temperature methyl-group dynamics.
2001 Feb
Pharmacodynamic effects and plasma pharmacokinetics of single doses of cetrorelix acetate in healthy premenopausal women.
2001 Feb
Biodistribution of radiolabeled [(3)H] CMT-3 in rats.
2001 Feb
Lipase-catalyzed irreversible transesterification of 1-(2-furyl)ethanol using isopropenyl acetate.
2001 Feb
Effect of acetate on glycogen replenishment in liver and skeletal muscles after exhaustive swimming in rats.
2001 Feb
Arginine catabolism by Thermanaerovibrio acidaminovorans.
2001 Feb 20
Computational studies on nonenzymatic and enzymatic pyridoxal phosphate catalyzed decarboxylations of 2-aminoisobutyrate.
2001 Feb 6
Clostridium hungatei sp. nov., a mesophilic, N2-fixing cellulolytic bacterium isolated from soil.
2001 Jan
Long-term stability characterization of a controlled release gastrointestinal therapeutic system coated with a cellulose acetate pseudolatex.
2001 Jan
A survey of lipolytic and glycolytic end-products in commercial Cheddar enzyme-modified cheese.
2001 Jan
Cation-exchange purification of mutagenized bovine beta-casein expressed in transgenic mouse milk: its putative Asn68-linked glycan is heterogeneous.
2001 Jan
In vitro mixed ruminal microorganism fermentation of whole cottonseed coated with gelatinized corn starch and urea.
2001 Jan
Teprenone promotes the healing of acetic acid-induced chronic gastric ulcers in rats by inhibiting neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues.
2001 Jan
Effect of ruminal vs postruminal administration of degradable protein on utilization of low-quality forage by beef steers.
2001 Jan
Determination of cilostazol and its metabolites in human urine by high performance liquid chromatography.
2001 Jan
Measurement of myocardial blood flow with PET using 1-11C-acetate.
2001 Jan
Expression of alpha-amylase gene in rat liver: liver-specific amylase has a high affinity to glycogen.
2001 Jan
Acetylcholinesterase assay for rapid expression screening in liquid and solid media.
2001 Jan
Immunobiology of the reproductive tract in a female baboon.
2001 Jan
Insecticidal activity of common reagents for insect foreign bodies of the ear.
2001 Jan
Physical stability of the blue pigments formed from geniposide of gardenia fruits: effects of pH, temperature, and light.
2001 Jan
N(delta)-(5-hydroxy-4,6-dimethylpyrimidine-2-yl)-l-ornithine, a novel methylglyoxal-arginine modification in beer.
2001 Jan
Structure and dynamics of high molecular weight glutenin subunits of durum wheat (Triticum durum) in water and alcohol solutions studied by electron paramagnetic resonance and circular dichroism spectroscopies.
2001 Jan
The metal binding properties of the CCCH motif of the 50S ribosomal protein L36 from Thermus thermophilus.
2001 Jan
New analogues of bradykinin containing a conformationally restricted dipeptide fragment in their molecules.
2001 Jan
Preparations, characterizations, and structures of (biimidazole)dihalobis(triphenylphosphine)rhenium(III) salts: strong ion-pairing and acid-base properties.
2001 Jan 1
Control of electrochemical reactions at the capillary electrophoresis outlet/electrospray emitter electrode under CE/ESI-MS through the application of redox buffers.
2001 Jan 15
Modelling the influence of pH and organic acid types on thermal inactivation of Bacillus cereus spores.
2001 Jan 22
Identification of lactic acid bacteria constituting the predominating microflora in an acid-fermented condiment (tempoyak) popular in Malaysia.
2001 Jan 22
Di-tert-butyl phosphate complexes of cobalt(II) and zinc(II) as precursors for ceramic M(PO3)2 and M2P2O7 materials: synthesis, spectral characterization, structural studies, and role of auxiliary ligands.
2001 Jan 29
[DOTA-bis(amide)]lanthanide complexes: NMR evidence for differences in water-molecule exchange rates for coordination isomers.
2001 Jan 5
Optimised determination of clobazam in human plasma with extraction and high-performance liquid chromatography analysis.
2001 Jan 5
[Acetyl starch as volume substitute, a possible alternative to HES].
2001 Jan 5
Evaluation of a novel vitamin E coated cellulosic membrane hollow fiber dialyzer.
2001 Jan-Feb
Metabolic fate of [14C]-ethanol into endothelial cell phospholipids including platelet-activating factor, sphingomyelin and phosphatidylethanol.
2001 Jan-Feb
S-methyl-N,N-diethylthiocarbamate sulfoxide elicits neuroprotective effect against N-methyl-D-aspartate receptor-mediated neurotoxicity.
2001 Jan-Feb
Salt accumulation resulting from base added for pH control, and not ethanol, limits growth of Thermoanaerobacteriumthermosaccharolyticum HG-8 at elevated feed xylose concentrations in continuous culture.
2001 Jan-Feb
Conversion of sugars to 1,2-propanediol by Thermoanaerobacterium thermosaccharolyticum HG-8.
2001 Jan-Feb
Production of ethanol and xylitol from corn cobs by yeasts.
2001 Mar
Acute and chronic toxicity of Potassium Chloride (KCl) and Potassium Acetate (KC(2)H(3)O(2)) to Daphnia similis and Ceriodaphnia dubia (Crustacea; Cladocera).
2001 Mar
Measurement of low picomolar levels of triamcinolone acetonide in human bronchoalveolar lavage fluid by gas chromatography-electron-capture negative-ion mass spectrometry.
2001 Mar 1
Patents

Sample Use Guides

To promote continuous contact, insert a wick of cotton saturated with the drug solution (Vosol). Keep the wick in for at least 24 hours and keep it moist by adding 3 to 5 drops of solution every 4 to 6 hours. The wick may be removed after 24 hours but the patient should continue to instill 5 drops of the drug solution 3 or 4 times daily thereafter, for as long as indicated.
Route of Administration: Otic (auricular)
In Vitro Use Guide
Curator's Comment: Hydroxocobalamin (OH-Cbl), when used to treat vitamin B12 deficiency, is better retained by the body than is cyanocobalamin (CN-Cbl), but the availability to cells has not been studied systematically. In a series of experiments, were compared the uptake and internalization of OH-Cbl and CN-Cbl bound to transcobalamin II (TCII) by a human cell model, the HeLa cell. TCII-OH-Cbl was: (1) taken up in larger amounts per unit time, (2) the greater uptake was not a consequence of more effective attachment to receptors of TCII-Cbl nor to a more rapid regeneration of receptors, (3) the difference was expressed during the phase of internalization of TCII-Cbl, (4) with CN-Cbl, the stages of binding to receptors plus internalization were more readily reversed, and (5) larger amounts of OH-Cbl were internalized and converted to active coenzyme forms of Cbl.
Acetic acid inhibited Saccharomyces cerevisiae growth. The minimum inhibitory concentration (MIC) of acetic acid for yeast growth was 0.6% w/v (100 mM).
Name Type Language
HYDROXOCOBALAMIN ACETATE
EP   MART.   USP-RS   VANDF   WHO-DD  
Common Name English
HYDROXOCOBALAMIN ACETATE [EP MONOGRAPH]
Common Name English
HYDROXOCOBALAMIN ACETATE [JAN]
Common Name English
HYDROXOCOBALAMIN ACETATE [VANDF]
Common Name English
HYDROXOCOBALAMIN ACETATE [MART.]
Common Name English
HYDROXOCOBALAMIN ACETATE [USP-RS]
Common Name English
ACETATOCOBALAMIN [MI]
Common Name English
Hydroxocobalamin acetate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C26017
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C77156
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
PRIMARY
DRUG BANK
DBSALT001895
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
PRIMARY
DAILYMED
S535M27N3Q
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
PRIMARY
PUBCHEM
131634603
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PRIMARY
DRUG CENTRAL
4644
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PRIMARY
EVMPD
SUB02579MIG
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PRIMARY
CAS
214142-68-4
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
NON-SPECIFIC SUBSTITUTION
ECHA (EC/EINECS)
245-019-7
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
PRIMARY
FDA UNII
S535M27N3Q
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
PRIMARY
RXCUI
236302
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
PRIMARY RxNorm
ChEMBL
CHEMBL2103737
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PRIMARY
CAS
22465-48-1
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
PRIMARY
EPA CompTox
DTXSID8046901
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PRIMARY
SMS_ID
100000089042
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PRIMARY
MERCK INDEX
m6116
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
PRIMARY Merck Index
RS_ITEM_NUM
1324308
Created by admin on Sat Dec 16 06:45:08 GMT 2023 , Edited by admin on Sat Dec 16 06:45:08 GMT 2023
PRIMARY