General
Preferred name
BUTALBITAL
Synonyms
Itobarbital ()
Tetrallobarbital ()
Butalbital ciii ()
Alisobumal ()
Allylbarbituric Acid ()
Sandoptal ()
Butalbital-d5 ()
Butalbital (CRM) ()
Butalbital-d5 (CRM) ()
P&D ID
PD010151
CAS
77-26-9
145243-96-5
Tags
natural product
drug
available
Approved by
FDA
First approval
1983
1976
Drug Status
illicit
approved
Drug indication
Headache
Anxiety disorder
Sedative-Hypnotic
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS Butalbital is a short to intermediate-acting barbiturate that reversibly depresses the activity of excitable tissues, including the central nervous system in a nonselective manner [A177754]. Barbiturates exhibit muscle-relaxing and anti-anxiety properties [A177763] and they are capable of producing all levels of CNS mood alteration from excitation to mild sedation, hypnosis, and deep coma [F4561]. The sedative dose of butalbital in nontolerant individuals is 5-100 mg and the hypnotic dose is 100-200 mg [T598]. Pain perception and reaction are relatively unimpaired until the moment of unconsciousness [A177754]. In some cases, an unwanted paradoxical response of excitement may be observed instead of sedation with barbiturate treatment, which may be due to their depressant effects on inhibitory centers of the CNS [A177754]. At sufficiently high therapeutic doses, barbiturates induce anesthesia; however, barbiturates are reported to lose their effectiveness for sleep induction and sleep maintenance after 2 weeks [F4561]. Barbiturates are habit-forming; they can produce tolerance and both dependence and addiction, which is partly explained by decreased drug concentration at the site of action due to enhanced drug metabolism by induced enzymes, or to cellular adaptive changes [A177754]. In addition, butalbital may lead to analgesic overuse headache [A177754]. ; ; While butalbital is expected to mediate similar actions as other members of the barbiturate drug class, the effects of butalbital in isolation are not well understood [A177763]. It is suggested that butalbital is added in combination products to antagonize the unwanted central stimulating effect of stimulatory ingredients such as caffeine [A177763]. Butalbital may decrease blood pressure and heart rate when administered at sedative and hypnotic doses [FDA Label].
MOA Butalbital is a CNS depressant that suppresses neuronal excitability, impulse conduction, and the release of neurotransmitters, similar to actions of other barbiturates [T598]. Barbiturates primarily mediate suppressive actions on polysynaptic neuronal responses by diminishing facilitation while enhancing inhibition [A177754]. Inhibition occurs at GABAergic synapses that express GABA-A receptors, which are transmembrane chloride ion channels that bind an inhibitory neurotransmitter GABA, barbiturates, benzodiazepines, neurosteroids, and ethanol [A177754]. Upon activation, GABA-A receptors allow Cl- influx and K+ efflux into the postjunctional terminal, resulting in inhibition of the postsynaptic neuron. It is suggested that barbiturates, including butalbital, enhances GABA binding to the GABA-A receptors [F4561] by binding to the α+/β− interface in the intracellular domain (ICD) as an allosteric modulator [A177829]. Additionally, barbiturates promote benzodiazepine binding to the receptor [A177754]. Barbiturates potentiate GABA-induced increases in chloride conductance and depress voltage-activated calcium currents while prolonging the duration of GABA-induced chloride channel opening [A177754]. Butalbital may also inhibit the excitatory effects mediated by AMPA receptors by reducing glutamate-induced depolarizations of the receptor [A177754]. It is also proposed that barbiturates and opioids may potentiate the analgesic effects of each other when co-administered, although there are inconsistencies across preclinical data [A177754].
INDICATION Indicated for the management of the symptom complex of tension (or muscle contraction) headache, when other non-opioid analgesics and alternative treatments are inadequate, in various combinations with acetaminophen, aspirin, caffeine, and codeine [FDA Label].
ROE Butalbital predominantly undergoes renal elimination with 59 to 88% of the total dose administered being excreted from the kidneys as unchanged parent drug or metabolites [FDA Label, L6121]. Urinary excretion products included parent drug (about 3.6% of the dose), 5-isobutyl-5-(2,3-dihydroxypropyl) barbituric acid (about 24% of the dose), 5-allyl-5(3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8%), products with the barbituric acid ring hydrolyzed with excretion of urea (about 14% of the dose), as well as unidentified materials [FDA Label]. Of the material excreted in the urine, 32% is conjugated [FDA Label]. Elimination is not complete within 24 hours, and the drug accumulates with frequent administration [A177754].
TOXICITY Reported oral TDLO (woman) is 400 mg/kg and subcutaneous LD50 in rat is 160 mg/kg [MSDS]. The lowest acute dose of butalbital alone associated with death in adults is 2.0 g [A177754]. Symptoms of acute barbiturate poisoning include drowsiness, confusion, coma, respiratory depression, hypotension, and shock. Due to the CNS depressant effects, an overdose of barbiturates may lead to death [FDA Label]. Barbiturates are also associated with withdrawal reactions, which may lead to death if severe [A177754].
METABOLISM Butalbital is expected to undergo nearly complete hepatic metabolism [A177754]. It primarily undergoes C5 oxidation to form 5-isobutyl-5-(2,3-dihydroxypropyl) barbituric acid, which is the major metabolite. Butalbital may also undergo omega-hydroxylation to form 5-allyl-5(3-hydroxy-2-methyl-1-propyl) barbituric acid [A177835, Label, T598].
ABSORPTION Butalbital gets readily and rapidly absorbed from the gastrointestinal tract [F4561]. The time to reach the peak plasma concentrations is reported to be approximately 2 hours [A177754]. Typical blood concentrations of butalbital peaked at 2.1 mg/L and declined to 1.5 mg/L at 24 hr [A177838]. Plasma concentrations of 10 to 20 μg/mL have been associated with toxicity; coma and fatalities have occurred with concentrations of 25 to 30 μg/mL [A177754].
HALF-LIFE The plasma half-life is about 35 hours. In a study of 5 healthy volunteers receiving 100 mg butalbital in combination with aspirin and caffeine, the mean plasma elimination half-life of butalbital was 61 hours, with the range of 35 to 88 hours [A177838, T598].
DESCRIPTION Butalbital is a barbiturate drug. (GtoPdb)
Compound Sets
15
Cayman Chemical Bioactives
15788
20091
15800
20092
ChEMBL Approved Drugs
CHEMBL454
ChEMBL Drugs
CHEMBL454
Drug Repurposing Hub
DrugBank
DB00241
DrugBank Approved Drugs
DB00241
DrugCentral
441
DrugCentral Approved Drugs
441
DrugMAP
DM9J04X
DrugMAP Approved Drugs
DM9J04X
DrugMatrix
Guide to Pharmacology
7138
NCATS Inxight Approved Drugs
KHS0AZ4JVK
Prestwick Chemical Library
ReFrame library
External IDs
32
Properties
(calculated by RDKit )
Molecular Weight
224.12
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
2
Rotatable Bonds
4
Ring Count
1
Aromatic Ring Count
0
cLogP
0.96
TPSA
75.27
Fraction CSP3
0.55
Chiral centers
0.0
Largest ring
6.0
QED
0.55
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Indication
headache, muscle relaxant
Target
CHRNA4, CHRNA7, GABRA1, GABRA2, GABRA3, GABRA4, GABRA5, GABRA6, GABRB1, GABRB2, GABRB3, GABRD, GABRE, GABRG1, GABRG2, GABRG3, GABRP, GABRQ, GRIA2, GRIK2
MOA
GABA Receptor antagonist
Therapeutic Class
Analgesics
Source data