Amobarbital

Amobarbital

Systematic (IUPAC) name
5-ethyl-5-(3-methylbutyl)-1,3-diazinane-2,4,6-trione
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	?
Legal status	CA: Schedule IV DE: Anlage III (Prescription only) Schedule II/Schedule III (US)
Routes of administration	Oral, IM, IV, Rectal
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Biological half-life	8–42 hours
Excretion	Renal
Identifiers
CAS Number	57-43-2 Y 64-43-7 (sodium salt)
ATC code	N05CA02 (WHO)
PubChem	CID: 2164
DrugBank	DB01351 Y
ChemSpider	2079 Y
UNII	GWH6IJ239E Y
KEGG	D00555 Y
ChEBI	CHEBI:2673 Y
ChEMBL	CHEMBL267894 Y
Chemical data
Formula	C11H18N2O3
Molecular mass	226.272
SMILES O=C1NC(=O)NC(=O)C1(CCC(C)C)CC
InChI InChI=1S/C11H18N2O3/c1-4-11(6-5-7(2)3)8(14)12-10(16)13-9(11)15/h7H,4-6H2,1-3H3,(H2,12,13,14,15,16) Y Key:VIROVYVQCGLCII-UHFFFAOYSA-N Y
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Amobarbital (formerly known as amylobarbitone or sodium amytal) is a drug that is a barbiturate derivative. It has sedative-hypnotic properties. It is a white crystalline powder with no odor and a slightly bitter taste. It was first synthesized in Germany in 1923. If amobarbital is taken for extended periods of time, physical and psychological dependence can develop. Amobarbital withdrawal mimics delirium tremens and may be life-threatening.

Pharmacology

In an in vitro study in rat thalamic slices amobarbital worked by activating GABA_A receptors, which decreased input resistance, depressed burst and tonic firing, especially in ventrobasal and intralaminar neurons, while at the same time increasing burst duration and mean conductance at individual chloride channels; this increased both the amplitude and decay time of inhibitory postsynaptic currents.

Amobarbital has been used in a study to inhibit mitochondrial electron transport in the rat heart.

A 1988 study found that amobarbital increases benzodiazepine receptor binding in vivo with less potency than secobarbital and pentobarbital (in descending order), but greater than phenobarbital and barbital (in descending order).

It has an LD₅₀ in mice of 212 mg/kg s.c.

Metabolism

Amobarbital undergoes both hydroxylation to form 3'-hydroxyamobarbital, and N-glucosidation to form 1-(beta-D-glucopyranosyl)amobarbital.

Indications

Approved

• Anxiety
• Epilepsy
• Insomnia
• Wada test

Unapproved/off-label

When given slowly by an intravenous route, sodium amobarbital has a reputation for acting as a so-called truth serum. Under the influence, a person will divulge information that under normal circumstances they would block. As such, the drug was first employed clinically by Dr. William Bleckwenn at the University of Wisconsin to circumvent inhibitions in psychiatric patients. The use of amobarbital as a truth serum has lost credibility due to the discovery that a subject can be coerced into having a "false memory" of the event.

The drug may be used intravenously to interview patients with catatonic mutism, sometimes combined with caffeine to prevent sleep.

It was used by the United States armed forces during World War II in an attempt to treat shell shock and return soldiers to the front-line duties. This use has since been discontinued as the powerful sedation, cognitive impairment, and dis-coordination induced by the drug greatly reduced soldiers' usefulness in the field.

Contraindications

A vial of amytal sodium

The following drugs should be avoided when taking amobarbital:

• Antiarrhythmics, such as verapamil and digoxin
• Antiepileptics, such as phenobarbital or carbamazepine
• Antihistamines, such as doxylamine and clemastine
• Antihypertensives, such as atenolol and propranolol
• Alcohol
• Benzodiazepines, such as diazepam, clonazepam or nitrazepam
• Caffeine
• Chloramphenicol
• Chlorpromazine
• Cyclophosphamide
• Ciclosporin
• Digitoxin
• Doxorubicin
• Doxycycline
• Methoxyflurane
• Metronidazole
• Narcotic analgesics, such as morphine and oxycodone
• Quinine
• Steroids, such as prednisone and cortisone
• Theophylline
• Warfarin

Interactions

Amobarbital has been known to decrease the effects of hormonal birth control, sometimes to the point of uselessness. Being chemically related to phenobarbital, it might also do the same thing to digitoxin, a cardiac glycoside.

Overdose

Some side effects of overdose include confusion (severe); decrease in or loss of reflexes; drowsiness (severe); fever; irritability (continuing); low body temperature; poor judgment; shortness of breath or slow or troubled breathing; slow heartbeat; slurred speech; staggering; trouble in sleeping; unusual movements of the eyes; weakness (severe).

Chemistry

Amobarbital (5-ethyl-5-isoamylbarbituric acid), like all barbiturates, is synthesized by reacting malonic acid derivatives with urea derivatives. In particular, in order to make amobarbital, α-ethyl-α-isoamylmalonic ester is reacted with urea (in the presence of sodium ethoxide).

Society and culture

It has been used to convict alleged murderers such as Andres English-Howard, who strangled his girlfriend to death but claimed innocence. He was surreptitiously administered the drug by his lawyer, and under the influence of it he revealed why he strangled her and under what circumstances. A year later he confessed on the witness stand and was convicted on the basis of these statements. He later committed suicide in his cell.

On the night of August 28, 1951, Robert Walker's housekeeper found the actor in an emotional state. She called Walker's psychiatrist who arrived and administered amobarbital for sedation. Walker was allegedly drinking prior to his emotional outburst, and it is believed the combination of amobarbital and alcohol resulted in a severe reaction. As a result, he passed out and stopped breathing, and all efforts to resuscitate him failed. Walker died at 32 years old.

See also

• Blue 88
• Depressant
• Tuinal