Pentobarbital

Nembutal · C07422 · Mebumal · Neodorm · Dorsital · Rivadorm · Ethaminal · Mebubarbital

Identifikatoren & physikalische Daten

CAS No.	76-74-4
Summenformel	C11H18N2O3
Durchschnittliche Molmasse	226,27 g/mol
Monoisotopische Masse	226,13174244 g/mol
SMILES	CCCC(C)C1(CC)C(=O)NC(=O)NC1=O
InChIKey	WEXRUCMBJFQVBZ-UHFFFAOYSA-N
PubChem CID	4737
ChEMBL	CHEMBL448
ChEBI	CHEBI:7983
EC No.	200-983-8
DTXSID	DTXSID7023435
Lokaler Name	Pentobarbital

Chemische & physikalische Eigenschaften

XLogP	2,1
Polarare Oberfläche (TPSA)	75,3
H-Brücken-Donoren	2
H-Brücken-Akzeptoren	3
Frei drehbare Bindungen	4
Schwere Atome	16
Formalladung	0
Komplexität	305
LogP (Verteilungskoeffizient)	2.1log Kow = 2.10
LogS	-2.52
Geruch	Practically odorless
Color/Form	Crystals from alcoholWhite to practically white, fine, powderNeedles from water
Löslichkeit	679A white, hygroscopic, crystalline powder or granules, odorless or with a slight characteristic odor, with a slightly bitter taste. Very sol in water and alcoholpractically insol in ether. A 10% soln in water has pH of 9.6 to 11 and slowly decomposes. /Pentobarbitone sodium/A fine, white, odorless, crystalline powder with a slightly bitter taste. Sparingly sol in waterslightly sol in alcoholpractically insol in ether. A saturated soln in water has a pH of about 9.5. /Pentobarbital calcium/Slightly soluble in watersoluble in ethanol, ethyl etherVery slightly soluble in water and carbon tetrachloridevery soluble in acetone and methyl alcohol1 part in 4.5 parts alcohol1 part in 4 parts chloroform1 part in 10 parts etherVery slightly soluble in water, freely soluble in ethanol. It forms water-soluble compounds with alkali hydroxides and carbonates and with ammonia.679 mg/L
Decomposition	When heated to decomposition it emits toxic fumes of /nitric oxide/.
Schmelzpunkt	129.5130 °C129.5 °C129.5°C
Physical Description	Solid
Stability/Shelf Life	Aqueous solutions of pentobarbital sodium are not stable, and solutions for injection should not be used if they contain a precipitate. The drug is more stable in propylene glycol, and this vehicle is used as a solvent in commercially available injections. Solutions of pentobarbital sodium should not be added to acidic solutions because precipitation of pentobarbital may occur. Pentobarbital sodium suppositories should be stored at 2-8 °C.Sensitive to air & moisture /Pentobarbital sodium/Alkaline soln decomp on storage & heating /Pentobarbital sodium/
Dissociation Constants	8.11 (at 25 °C)pK value = 7.88 (Metabolic)Soln is alkaline to litmus & to phenolphthaleinpKa1: 8.17pKa2: 12.67 /Pentobarbital sodium/
Kovats Retention Index	1740171117161711.5172017321763172117331770173017351779.7176117581786.41755.51766.61754.21734.21772
Other Experimental Properties	The pK values of the hypnotically active barbituric acids range between 7.78 and 8.30. Disubstituted barbituric acids are present, to ca. 50 %, in the undissociated form under physiological conditions (pH 7.4). Only this form of the drug can pass through biological membranes. The degree of dissociation is strongly influenced by slight alterations in pH.A polymorphic form may occur, with a mp of about 115 °Cit gradually reverts to the more stable form on heating at about 110 °C.White powderslightly bitter taste. Decomp at about 127 °C. Freely soluble in water, alcohol. Practically insoluble in benzene, ether. Aqueous solutions are unstable. /Pentobarbital sodium/
Siedepunkt	367.89°C (rough estimate)
Dichte	1.1376 (rough estimate)
Brechungsindex	1.4620 (estimate)
Flammpunkt	9℃
Lagerbedingungen	2-8°C
pKa (Säurekonstante)	pK1:8.11(0) (25°C)
Aggregatzustand	A neat solid
Henry-Konstante	1.2×107 mol/(m3Pa) at 25℃, HSDB (2015)
CAS Datenbank	76-74-4(CAS DataBase Reference)
NIST chemische Informationen	Pentobarbital(76-74-4)
EPA chemische Informationen	Pentobarbital (76-74-4)

Sicherheit & Vorschriften

GHS-Einstufung	DangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]H361 (95.3%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 43 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.
Regulatorische Informationen	DEA schedule II controlled substanceDEA schedule III controlled substanceStatus: Active Update: 11-10-2012 https://echa.europa.eu/registration-dossier/-/registered-dossier/11117
Weitere Sicherheitsinformationen	IMAP assessments - 2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-ethyl-5-(1-methylbutyl)-: Environment tier I assessmentIMAP assessments - 2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-ethyl-5-(1-methylbutyl)-: Human health tier I assessment
FDA-Anforderungen	The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, including pentobarbital, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Pentobarbital is included on this list.The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Pentobarbital sodium is included on this list. /Pentobarbital sodium/Sodium pentobarbital injection. ... The drug is indicated for use as a general anesthetic in dogs and cats. Although it may be used as a general surgical anesthetic for horses, it is usually given at a lower dose to cause sedation and hypnosis and may be supplemented with a local anesthetic. It may also be used in dogs for the symptomatic treatment of strychnine poisoning. /Sodium pentobarbital/For more FDA Requirements (Complete) data for Pentobarbital (7 total), please visit the HSDB record page.
Special Reports	DHHS/NIDAResearch Monograph Series 52: Testing Drugs for Physical Dependence Potential and Abuse Liability (1984) DHHS Pub No. (ADM)87-1332[Available from, as of March 29, 2010: http://www.nida.nih.gov/pdf/monographs/download52.html]Research Monograph Series 54: Mechanisms of Tolerance and Dependence (1984) DHHS Pub No. (ADM)88-1330[Available from, as of March 29, 2010: http://www.nida.nih.gov/pdf/monographs/download54.html]Research Monograph Series 56: Etiology of Drug Abuse: Implications for Prevention (1987) DHHS Pub No. (ADM)87-1335[Available from, as of March 29, 2010: http://www.nida.nih.gov/pdf/monographs/download56.html]Research Monograph Series 59: Current Research on the Consequences of Maternal Drug Abuse (1985) DHHS Pub No. (ADM)85-1400[Available from, as of March 29, 2010: http://www.nida.nih.gov/pdf/monographs/monograph59/download59.html]For more Special Reports (Complete) data for Pentobarbital (8 total), please visit the HSDB record page.
Hazard Classes and Categories	Acute Tox. 3 (100%)Repr. 2 (95.3%)
Skin, Eye, and Respiratory Irritations	May cause irritation. Remove to fresh air. Flush with copious quantities of water.
Brandbekämpfungsverfahren	Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials.As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.
Lagerbedingungen	Store in tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity.Pentobarbital sodium injection should be stored at room temperaturefreezing and exposure of the injection to extreme heat should be avoided. Brief exposure to temperatures up to 40 °C will not adversely affect the injection.
Reinigungsverfahren	Wipe up spillage or collect spillage using a high- efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site.
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.SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.
Preventive Measures	This material is assumed to be combustible. As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.As a general rule, when handling USP Reference Standards avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling./Use/ safety goggles /and/ protect exposed skin.
Personal Protective Equipment (PPE)	Engineering controls such as exhaust ventilation are recommended.Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used.
Treatment	Treatment of overdosage is mainly supportive and consists of maintaining an adequate airway, with assisted respiration and oxygen administration as necessary, monitoring of vital signs and fluid balance, and fluid therapy and other standard treatment for shock, if needed. If renal function is normal, forced diuresis may aid in the elimination of the barbiturate. Alkalinization of the urine increases renal excretion of some barbiturates, especially phenobarbital, also aprobarbital and mephobarbital (which is metabolized to phenobarbital). Although not recommended as a routine procedure, hemodialysis may be used in severe barbiturate intoxications or if the patient is anuric or in shock. The patient should be rolled from side to side every 30 minutes and antibiotics should be given if pneumonia is suspected. Appropriate nursing care to prevent hypostatic pneumonia, decubiti, aspiration, and other complications of patients with altered states of consciousness. (L1712)
Wechselwirkungen	Acute dosage of mice with DDT prolonged pentobarbitone sleeping time, with inhibition of barbiturate metabolism, but chronic dosage of mice or rats shortened sleeping time because of enzyme induction.Pentobarbital & streptomycin interact to induce vasodilation in the perfused kidney & other vessels of the dog.During evaluations of a vaccine of killed suspensions of Corynebacterium parvum, iv injections of Corynebacterium parvum in mice rendered them lethally sensitive to normal safe anesthetic doses of pentobarbitone. Caution was recommended when both preparations might be used in man.Therapeutic effects of acetaminophen may be decreased when the medication is used concurrently in patients receiving chronic barbiturate therapy because of increased metabolism resulting from induction of hepatic microsomal enzymesrisk of hepatotoxicity with single toxic doses or prolonged use of high doses of acetaminophen may be increased in alcoholics or in patients regularly using hepatic enzyme inducers such as barbiturates. /Barbiturates/For more Interactions (Complete) data for Pentobarbital (42 total), please visit the HSDB record page.
Gesundheitliche Auswirkungen	They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.
Umweltverhalten	TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 28(SRC), determined from a log Kow of 2.10(2) and a regression-derived equation(3), indicates that pentobarbital is expected to have very high mobility in soil(SRC). The pKa of pentobarbital is 7.8(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 the neutral species from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 8.4X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Pentobarbital is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(7). Biodegradation data were not available(SRC, 2009).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 28(SRC), determined from a log Kow of 2.10(2) and a regression-derived equation(3), indicates that pentobarbital 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 8.4X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 11(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2009).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), pentobarbital, which has an estimated vapor pressure of 3.0X10-10 Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase pentobarbital may be removed from the air by wet or dry deposition(SRC). Pentobarbital does not contain chromophores that absorb at wavelengths >290 nm(3) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).
Unerwünschte Wirkungen	The main adverse reactions surrounding pentobarbital use are CNS effects, including altered mental status, agitation, confusion, drowsiness, respiratory depression, bradycardia, hypotension, cardiovascular collapse, and syncope. Other significant adverse effects to be aware of include hallucinations, headache, insomnia, nausea, vomiting, hepatoxicity, megaloblastic anemia, angioedema, local injection site reactions, laryngospasm, bronchospasm, apnea, and hyperkinesia. At high doses of pentobarbital, total loss of neurological function is observed.Drug-Drug InteractionsPentobarbital interacts with several major classes of drugs and requires close monitoring to maintain therapeutic drug levels. As a class, barbiturates induce hepatic microsomal enzymes, which increase the rate of metabolism of other drugs metabolized by these hepatic enzymes. In particular, anticoagulants can be affected, and patients taking these drugs, predominantly warfarin, may require dosage adjustments. Other drug interactions to be aware of include levothyroxine, corticosteroids, doxycycline, phenytoin, valproic acid, alcohol, monoamine oxidase inhibitors (MAOIs), and some hormones such as estradiol, estrone, and progesterone.Barbiturates can decrease the absorption of griseofulvin. Concomitant administration requires dose adjustment. Barbiturates combined with CNS depressants such as benzodiazepines and opioids can lead to profound respiratory depression. Misusing kratom with barbiturates can lead to severe CNS depression and death.
Expositionspfade	Barbiturates are absorbed in varying degrees following intravenous, oral, rectal, or parenteral administration.
Milk Concentrations	Pentobarbital is excreted into breast milk. Breast milk levels of 0.17 ug/mL have been detected 19 hours after a dose of 100 mg daily for 32 days.
Toxizitätsübersicht	Pediatric neurotoxicity is reported with the use of pentobarbital. Barbiturates, including pentobarbital, can increase GABA activity, leading to increased neuronal apoptosis and impaired cognition when used for more than 3 hours. Treatment of pentobarbital toxicity involves supportive care, as no antidote exists. Overdose can lead to airway compromise, cardiovascular collapse, coma, and death. Treatment often requires intubation, hemodynamic support with vasopressors, and maintaining body temperature with warmers, commonly in an intensive care unit (ICU) setting. In mild or early cases of toxicity, activated charcoal and alkaline diuresis have been added but show minimal benefits. Always contact poison control if poisoning or overdose is suspected.Caution is warranted for individuals with renal and hepatic impairment. While the manufacturer does not offer specific dosage adjustment recommendations for renal impairment, monitoring kidney function when administering high doses or conducting prolonged treatment is crucial. Comparable effects are observed in individuals with hepatic impairment, necessitating close patient monitoring. Continuous venovenous hemofiltration is known to enhance the removal of pentobarbital.Pentobarbital binds at a distinct binding site associated with a Cl- ionopore at the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged. All of these effects are associated with marked decreases in GABA-sensitive neuronal calcium conductance (gCa). The net result of barbiturate action is acute potentiation of inhibitory GABAergic tone. Barbiturates also act through potent (if less well characterized) and direct inhibition of excitatory AMPA-type glutamate receptors, resulting in a profound suppression of glutamatergic neurotransmission.
Signs and Symptoms	Symptoms of an overdose typically include sluggishness, incoordination, difficulty in thinking, slowness of speech, faulty judgment, drowsiness or coma, shallow breathing, staggering, and in severe cases coma and death.
Soil Adsorption/Mobility	The Koc of pentobarbital is estimated as 28(SRC), using a log Kow of 2.10(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that pentobarbital is expected to have very high mobility in soil. The pKa of pentobarbital is 7.8(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). The pK values of the hypnotically active barbituric acids range between 7.78 and 8.30. Disubstituted barbituric acids exist in the undissociated form at pH 7.4 and the degree of dissociation is strongly influenced by slight alterations in pH(4).
Human Toxicity Excerpts	/HUMAN EXPOSURE STUDIES/ To investigate the effect of sedative agents on visual processing in humans, /investigators/ analysed the BOLD contrast signal response to a visual stimulation paradigm in 15 healthy, adult volunteers using functional magnetic resonance imaging. The subjects were tested during alert state and under sedation following intravenous administration of pentobarbital. The injection of pentobarbital not only significantly reduced the response signal strength but the reduction in BOLD contrast signal was related to the ratio of amount of sedative administered and the subject's body weight. The three subjects with the highest relative sedative dosage even displayed an inverted (negative) BOLD contrast signal. A significant reduction in the number of positively correlating pixels was found 15 min after administration of pentobarbital. All measured parameters returned to near pre-sedative levels by the end of the experimental session. The relative dosage dependence of the strength of the BOLD signal the negative BOLD signal in the three subjects with the highest relative sedative dosage indicates that pentobarbital had a more pronounced effect on cerebral blood flow than on cerebral oxidative metabolism./HUMAN EXPOSURE STUDIES/ /Investigators/hypothesized that pentobarbital would improve upper airway mechanics based on an increase in: a) latency to arousal, b) amplitude of the phasic genioglossus electromyogram, and decrease in: c) the active upper-airway critical closing pressure (Pcrit).Twelve healthy subjects received pentobarbital 100 mg or placebo in a double-blind, cross-over protocol. During wakefulness, /investigators/ measured the genioglossus reflex response to negative-pressure pulses. During sleep, carbon dioxide was insufflated into the inspired air. Airway pressure was then decreased in a stepwise fashion until arousal from sleep.With basal breathing during sleep, flow-rate was lower in volunteers given pentobarbital, end-tidal carbon dioxide concentration and upper airway resistance were greater, and Pcrit was unaffected (pentobarbital: -11.7+/-4.5 vs. placebo: -10.25+/-3.6 cm H2O, p=0.11). Pentobarbital increased the time to arousal (297+/-63s vs. 232+/-67s p<0.05), at which time phasic genioglossus EMG was higher (6.2+/-4.8 %max vs. 3.1+/-3%, respectively, p<0.05) as were carbon dioxide levels. The increase in genioglossus electromyogram after carbon dioxide administration was greater after pentobarbital vs. placebo. Pentobarbital did not affect the genioglossus negative pressure reflex.Pentobarbital increases the time to arousal and stimulates genioglossus muscle activity, but it increases upper airway resistance during sleep./SIGNS AND SYMPTOMS/ Complications such as pneumonia, pulmonary edema, cardiac arrhythmias, congestive heart failure, and renal failure may occur. Uremia may increase CNS sensitivity to barbiturates./SIGNS AND SYMPTOMS/ In extreme overdose, all electrical activity in the brain may cease, in which case a "flat" EEG normally equated with clinical death cannot be accepted. This effect is fully reversible unless hypoxic damage occurs. Consideration should be given to the possibility of barbiturate intoxication even in situations that appear to involve trauma.For more Human Toxicity Excerpts (Complete) data for Pentobarbital (17 total), please visit the HSDB record page.
Artificial Pollution Sources	Pentobarbital's production and use as a sedative(1) may result in its release to the environment through various waste streams(SRC).
Wassergefährdungsklasse (WGK)	3
UN-Transportnummer	UN 2811 6.1/PG 3
Zollcode	2933530000
RTECS-Nr.	CQ5775000
R-Sätze (R)	25-63-39/23/24/25-36/38-23/24/25-11
Toxizität	A barbiturate that causes CNS depression, apparently due to a facilitation of GABA-ergic inhibition. It appears that the site of action of pentobarbital may be the macromolecular complex made up of a GABA receptor, chloride channel, benzodiazepine-binding site, and picrotoxin-binding site. Barbiturates have been shown to compete for dihydropicrotoxinin-binding sites. In clinical use, barbiturates such as pentobarbital have been largely replaced as sedative-hypnotics by the much safer benzodiazepines. The sedative-hypnotic properties of barbiturates may lead to abuse, as tolerance and dependence are known to occur. In animals, pentobarbital is routinely used for its anesthetic and anticonvulsant properties, as well as for euthanasia. Pentobarbital, like other barbiturates, can induce the metabolism of other compounds by altering cytochrome P450 activity. The oral LD50 in rats is 118 mg/kg.
Gefahrensymbole	T,F
Sicherheitshinweise (S)	7-16-36/37-45-36/37/39-22
Gefahrenklasse	6.1(b)
Verpackungsgruppe	III
Gefahrstoffdaten	76-74-4(Hazardous Substances Data)

Anwendungen & Verwendung

Beschreibung

Pentobarbital (CRM) (Item No. 20966) is a certified reference material categorized as a barbiturate. Pentobarbital is regulated as a Schedule II compound in the United States. Pentobarbital (CRM) (Item No. 20966) is provided as a DEA exempt preparation. This product is intended for research and forensic applications.

Verwenden

Sedative-hypnotic.