Ketamine hydrochloride CAS 1867-66-9
Introduction：Basic information about Ketamine hydrochloride CAS 1867-66-9, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Ketamine hydrochloride Basic information
| Product Name: | Ketamine hydrochloride |
| Synonyms: | (+-)-2-(o-chlorophenyl)-2-(methylamino)cyclohexanonehydrochloride;2-(2-chlorophenyl)-2-(methylamino)-,hydrochloride,(+-)-cyclohexanon;2-(o-chlorophenyl)-2-(methylamino)cyclohexanonehydrochloride;ketalar;ketanest;ketaset;ketavet;ketavet100 |
| CAS: | 1867-66-9 |
| MF: | C13H16ClNO.ClH |
| MW: | 274.19 |
| EINECS: | 217-484-6 |
| Product Categories: | Glutamate receptor;Amines;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;chemical research;medicine grade;pharmaceutical intermediate |
| Mol File: | 1867-66-9.mol |
Ketamine hydrochloride Chemical Properties
| Melting point | 252-254°C |
| Fp | 9℃ |
| storage temp. | 2-8°C |
| solubility | H2O: 200 mg/mL |
| form | solid |
| pka | 7.5(at 25℃) |
| color | white |
| Water Solubility | Soluble to 100 mM in water |
| CAS DataBase Reference | 1867-66-9(CAS DataBase Reference) |
| EPA Substance Registry System | Ketamine hydrochloride (1867-66-9) |
Safety Information
| Hazard Codes | Xn,T,F |
| Risk Statements | 22-36/37/38-39/23/24/25-23/24/25-11 |
| Safety Statements | 26-45-36/37-16-7 |
| RIDADR | 3249 |
| WGK Germany | 3 |
| RTECS | GW1400000 |
| HazardClass | 6.1(b) |
| PackingGroup | III |
| HS Code | 2923900100 |
| Toxicity | LD50 in adult mice, rats (mg/kg): 224 ±4, 229 ±5 i.p. (Goldenthal) |
| Chemical Properties | Ketamine hydrochloride is Off-White Solid |
| Originator | Ketanest,Parke Davis,W. Germany,1969 |
| Uses | Anesthetic (intravenous). Controlled substance (depressant). |
| Definition | ChEBI: The hydrochloride salt of ketamine. |
| Definition | ketamine: A vetinary anaesthetic that is used illegally as a club drug. Itis a class A drug in the UK. |
| Manufacturing Process | The 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone N-methylimine used as anintermediate is prepared as follows. To the Grignard reagent prepared from119.0 g of cyclopentyl bromide and 19.4 g of magnesium is added 55.2 g ofo-chlorobenzonitrile. The reaction mixture is stirred for 3 days and thereafterhydrolyzed in the usual manner. From the hydrolysis there is obtained ochlorophenylcyclopentylketone, BP 96° to 97°C (0.3 mm), nD251.5452. To21.0 g of the ketone is added 10.0 g of bromine in 80 ml of carbontetrachloride. 1-Bromocyclopentyl-(o-chlorophenyl)-ketone, BP 111° to 114°C (0.1 mm) isisolated in the usual manner. Since it is unstable, it must be usedimmediately. The bromoketone (29.0 g) is dissolved in 50 ml of liquidmethylamine. After one hour, the excess liquid methylamine is allowed toevaporate. The organic residue is dissolved in pentane, and upon evaporationof the solvent, 1-hydroxycyclopentyl-(o-chlorophenyl)-ketone N-methylimine,MP 62°C, is isolated. 1-Hydroxycyclopentyl-(o-chlorophenyl)-ketone N-methylimine (2.0 g) isdissolved in 15 ml of Decalin and refluxed for 2,5 hours. After evaporation ofthe Decalin under reduced pressure, the residue is extracted with dilutehydrochloric acid, the solution treated with decolorizing charcoal, and theresulting acidic solution is made basic. The liberated product, 2-methylamino-2-(o-chlorophenyl)-cyclohexanone, after crystallization from pentane-ether,has MP 92° to 93°C. The hydrochloride of this compound has MP 262° to263°C. |
| Brand name | Ketalar (Parkdale). |
| Therapeutic Function | Anesthetic |
| Biological Functions | Ketamine is a cyclohexanone derivative whose pharmacologicalactions are quite different from those of theother IV anesthetics. The state of unconsciousness itproduces is trancelike (i.e., eyes may remain open untildeep anesthesia is obtained) and cataleptic; it has frequentlybeen characterized as dissociative (i.e., the patientmay appear awake and reactive but does not respondto sensory stimuli). The term dissociativeanesthesia is used to describe these qualities of profoundanalgesia, amnesia, and superficial level of sleep. |
| General Description | Ketamine is formulated as an acidic solution, pH 3.5 to 5.5,available with or without 0.1 mg/mL benzethonium chloridepreservative. Ketamine is marketed as the racemic mixtureand some properties of the individual isomers have beenelucidated. Ketamine is a rapid-acting agent that can beused for induction, used as the sole agent for general anesthesiaor combined with other agents. Unlike the proposedmechanism of action for most anesthetics, ketamine doesnot act at the GABAA receptor. Ketamine acts as a noncompetitiveantagonist at the glutamate, NMDA receptor, anonspecific ion channel receptor. The NMDA receptor is locatedthroughout the brain and contains four well-studiedbinding sites. The primary binding site binds L-glutamate,NMDA, and aspartate. The allosteric site binds glycine,which facilitates primary ligand binding. There is also amagnesium binding site that blocks ion flow through thechannel and a phencyclidine (PCP) binding site that blocksthe ion channel when occupied. Ketamine is believed tobind to the PCP site in a stereoselective manner and blockthe ion flow in the channel. By blocking the flow ofcalcium ions into the cell, ketamine prevents the calcium concentration from building and triggering excitatorysynaptic transmissions in the brain and spinal cord. |
| Biological Activity | Non-competitive NMDA receptor antagonist (EC 50 values are 13.6 and 17.6 μ M for NR1/NR2A and NR1/NR2B subunit combinations respectively). Dissociative anesthetic. |
| Biochem/physiol Actions | Selective NMDA glutamate receptor antagonist; veterinary anesthetic. |
| Pharmacology | Slow IV administration of ketamine does not causegradual loss of airway reflexes, apnea, or general muscularrelaxation.The onset of the ketamine-induced “anestheticstate” is accompanied by a gradual, mild increasein muscle tone (which greatly resembles catatonia), continuedmaintenance of pharyngeal and laryngeal reflexes,and opening of the eyes (usually accompanied bynystagmus). Although reflexes may be maintained, theairway still must be protected, since ketamine sensitizeslaryngeal and pharyngeal muscles to mucous or foreignsubstances, and laryngospasm may occur. Ketamine also can be contrasted to other intravenousdrugs in its ability to cause cardiovascular stimulationrather than depression. The observed increasesin heart rate and blood pressure appear to be mediatedthrough stimulation of the sympathetic nervous system.In a healthy, normovolemic, unpremedicated patient,the initial induction dose of ketamine maintains or stimulatescardiovascular function. In contrast, patients with poor cardiac reserve, compromised autonomic control,or hypovolemia may undergo a precipitous fall in bloodpressure after induction of anesthesia with ketamine. Ifselection of the patient and preoperative preparationare carefully done, however, ketamine may be an excellentdrug for the induction of anesthesia in individualswho cannot tolerate compromise of their cardiovascularsystem. The analgesia induced by ketamine also is a propertythat separates it from other IV anesthetic drugs.Analgesia is obtained without a deep level of anesthesia.When subdissociative doses of ketamine are giveneither IV or intramuscularly (IM), they provide adequateanalgesia for postoperative pain relief as well asanalgesia for brief operations on the skin, such as debridementof third-degree burns. Because it can be regardedas a nearly complete anesthetic (hypnosis andanalgesia), does not require anesthesia equipment, andis relatively protective of hemodynamics, ketamine alsocan be very useful outside of normal operating roomconditions, such as may be found during painful radiographicprocedures. A most important advantage of ketamine over otheranesthetic agents is its potential for administration bythe IM route.This is particularly useful in anesthetizingchildren, since anesthesia can be induced relativelyquickly in a child who resists an inhalation induction orthe insertion of an IV line. Ketamine has a limited butuseful role as an IM induction agent and in pediatrics. |
| Clinical Use | Like other dissociative anesthetics, ketamine isabused for its hallucinatory effects. Most of the illegallyused ketamine comes from stolen legitimate sources, particularlyfrom veterinary clinics or smuggled in fromMexico. Ketamine is metabolized via N-demethylation to formthe main metabolite norketamine. Norketamine has aboutone third the potency of the parent compound. Minor metabolicpathways include hydroxylation of the cyclohexanonering; hydroxylation followed by glucuronide conjugation,and hydroxylation followed by dehydration to the cyclohexenonederivative. |
| Side effects | The most serious disadvantage to the use of ketamine isits propensity to evoke excitatory and hallucinatoryphenomena as the patient emerges from anesthesia.Patients in the recovery period may be agitated, screamand cry, hallucinate, or experience vivid dreams. Theseepisodes may be controlled to some extent by maintaininga quiet reassuring atmosphere in which the patientcan awaken or if necessary by administering tranquilizingdoses of diazepam. Other reported side effects include vomiting, salivation,lacrimation, shivering, skin rash, and an interactionwith thyroid preparations that may lead to hypertensionand tachycardia. Ketamine also may raise intracranialpressure and elevate pulmonary vascular resistance, especiallyin children with trauma or congenital heart disease.Increases in intraocular pressure also may occur,and vigilance is required if ketamine is used in ocularsurgery. |
| Safety Profile | Poison by intramuscular, intraperitoneal, and intravenous routes. Moderately toxic by ingestion. Human systemic effects by intravenous and possibly other routes: analgesia, coma, hallucinations and distorted perceptions, dyspnea. An experimental teratogen. An anesthetic. When heated to decomposition it emits very toxic fumes of Cland NOx. |
| Drug interactions | Potentially hazardous interactions with other drugs Adrenergic-neurone blockers: enhanced hypotensive effect. Antihypertensives: enhanced hypotensive effect. Antidepressants: stop MAOIs 2 weeks before surgery; increased risk of arrhythmias and hypotension with tricyclics. Antipsychotics: enhanced hypotensive effect. Memantine: increased risk of CNS toxicity, avoid concomitant use. Muscle relaxants: enhances effects of atracurium. |
| storage | Store at RT |
Ketamine hydrochloride Preparation Products And Raw materials
| Raw materials | Pentane-->Activated carbon,decolor-->2-Chlorobenzoic acid-->Cyclopentene-->Decahydronaphthalene-->Chlormezanone-->Magnesium-->Bromocyclopentane-->2-Chlorobenzonitrile-->Methylamine |
| Preparation Products | (S)-(+)-Ketamine hydrochloride |
