Secobarbital
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Mechanism of action
Secobarbital binds at a distinct binding site associated with a Cl<sup>-</sup> ionopore at the GABA<sub>A</sub> receptor, increasing the duration of time for which the Cl<sup>-</sup> ionopore is open. The post-synaptic inhibitory effect of GABA in the thalamus is, therefore, prolonged.
The exact mechanism(s) by which barbiturates exert their effect on the CNS, has not been fully elucidated. However, it is believed that such effects are related, at least partially, to the drugs' ability to enhance the activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the CNS, by altering inhibitory synaptic transmissions that are mediated by GABA receptors. /Barbiturates General Statement/
Although the drugs act throughout the CNS, a site of particular sensitivity is the polysynaptic midbrain reticular formation which is concerned with the arousal mechanism. Barbiturates induce an imbalance in central inhibitory and facilitatory mechanisms influencing the cerebral cortex and the reticular formation. The significance of the effect of barbiturates on neurotransmitters is unclear. It appears that the drugs decrease the excitability of both presynaptic and postsynaptic membranes. It has not been determined which of the various actions of barbiturates at cellular and synaptic levels are responsible for their sedative and hypnotic effects. /Barbiturates General Statement/
Relatively low doses of the barbiturates depress the sensory cortex, decrease motor activity, and produce sedation and drowsiness. In some patients, however, drowsiness may be preceded by a period of transient elation, confusion, euphoria, or excitement, especially after subhypnotic doses of aprobarbital, pentobarbital, or secobarbital. /Barbiturates General Statement/
Larger doses distort judgment, cloud perception, suppress motor activity, and produce drowsiness and sleep. Still larger doses induce anesthesia. Barbiturate-induced sleep differs from physiologic sleep. Barbiturates reduce the rapid eye movement (REM) or dreaming stage of sleep. Stages III and IV sleep are also decreased. Although tolerance develops to the REM-suppressant effects during chronic administration, REM rebound occurs when the drugs are withdrawn, and the patient may experience markedly increased dreaming, nightmares, and/or insomnia. /Barbiturates General Statement/
For more Mechanism of Action (Complete) data for Secobarbital (15 total), please visit the HSDB record page.
Pharmacodynamics
Secobarbital, a barbiturate, is used for the induction of anesthesia prior to the use of other general anesthetic agents and for induction of anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.
Pharmacokinetics
Half-life
The plasma half-life for secobarbital sodium in adults ranges between 15 to 40 hours, with a mean of 28 hours.
Secobarbital has an elimination half-life of about 30 hours.
Absorption
Barbiturates are metabolized primarily by the hepatic microsomal enzyme system, and the metabolic products are excreted in the urine and, less commonly, in the feces.
Approximately 90% of an oral dose of secobarbital is absorbed from the GI tract within 2 hours after ingestion, and peak plasma concentrations are reached within 2-4 hours. Virtually all of the drug is absorbed following rectal administration.
Plasma secobarbital concentrations of 1-5 ug/mL generally produce sedation, and plasma concentrations of 5-15 ug/mL produce sleep in most patients; however, plasma concentrations of greater than 10 ug/mL may produce coma. Plasma concentrations in excess of 30 ug/mL are potentially lethal.
When hypnotic doses of secobarbital are administered orally, the onset of action usually occurs within 15 minutes. Full hypnotic effect of the drug usually occurs 15-30 minutes following oral or rectal administration, 7-10 minutes following im administration, and 1-3 minutes following iv administration. (Rectal and parenteral preparations of the drug are no longer commercially available in the US.) The duration of the hypnotic effect is 1-4 hours following oral or rectal administration of an average dose of secobarbital and about 15 minutes following iv administration of a 100- to 150-mg dose.
Approximately 30-45% of the drug is bound to plasma proteins.
For more Absorption, Distribution and Excretion (Complete) data for Secobarbital (18 total), please visit the HSDB record page.
Metabolism
Secobarbital is metabolized by the liver via penultimate oxidation of the 1-methylbutyl substituent to form 5-allyl-5(3'-hydroxy-1'-methylbutyl)barbituric acid (hydroxysecobarbital), the major metabolite. Oxidation of the allyl substituent may also occur to form 5-[2',3'-dihydroxypropyl-5-(1'-methylbutyl)]barbituric acid (secodiol). These inactive metabolites are excreted in urine unchanged or as glucuronide conjugates. Hydroxysecobarbital may also be further oxidized to a ketone or a carboxylic acid. The allyl substituent at C 5 may be removed, and small quantities of the resulting 5-(1'-methylbutyl)barbituric acid metabolite have been found in urine.
Differences were observed in urine profiles from the rat and guinea pig following ip admin of secobarbital. ... The rat hydroxylated secobarbital on the side-chain and produced only a small amount of the diol, a product of epoxidation and hydrolysis of the allyl side-chain. These metabolites were excreted in almost equal quantities by the guinea pig. The ratio of metabolites was independent of the dose in the range 20-100 mg/kg-l in the rat. Doses over 50 mg/kg-l were lethal in the guinea pig.
Both the allyl and sec-amyl side-chains undergo metabolism to give mainly seconal diol and 2 diastereoisomers of hydroxyseconal, in man and dog; and hydroxyseconal and seconal carboxylic acid in rabbit.
In dogs and in man, secobarbital ... is metabolized into 5-(2,3-dihydroxypropyl)-5-(1-methylbutyl)barbituric acid and (+-)5-allyl-5-(3-hydroxy-1-methylbutyl)barbituric acid ... 5-(1-methylbutyl)barbituric acid was found in urine of some human subjects and ... in extracts from the liver of a suicide.
For more Metabolism/Metabolites (Complete) data for Secobarbital (7 total), please visit the HSDB record page.
Route of Elimination: Barbiturates are metabolized primarily by the hepatic microsomal enzyme system, and the metabolic products are excreted in the urine and, less commonly, in the feces.
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Fact-sheets from PsychonautWiki. Harm-reduction reference only — not medical advice.