Butalbital is a barbiturate drug used for symptomatic treatment of tension-type headache in various combinations with acetaminophen, aspirin, caffeine, and codeine. It can be found under various brand names including Allzital, Ascomp, Bupap, Butapap, Esgic, Fioricet, Fioricet With Codeine, Fiorinal, Orbivan, Tencon, Trianal, Trianal C, Vanatol, Vanatol S, Vtol, and Zebutal. Butalbital, or 5-allyl-5-isobutylbarbituric acid, is a derivative of barbituric acid which the hydrogens at position 5 are substituted by an allyl group and an isobutyl group. It is a short-to-intermediate acting member of barbiturates that exhibit muscle-relaxing and anti-anxiety properties that produce central nervous system (CNS) depression that ranges from mild sedation to general anesthesia. Butalbital has a low degree of selectivity and a narrow therapeutic index. Typically indicated to manage tension (or muscle contraction) headaches, butalbital is often combined with one or more therapeutic agents, such as acetylsalicylic acid, acetaminophen, aspirin, and caffeine. Butalbital is a CNS depressant that suppresses neuronal excitability, impulse conduction, and the release of neurotransmitters, similar to actions of other barbiturates. Barbiturates primarily mediate suppressive actions on polysynaptic neuronal responses by diminishing facilitation while enhancing inhibition. 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. 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 by binding to the α+/β− interface in the intracellular domain (ICD) as an allosteric modulator. Additionally, barbiturates promote benzodiazepine binding to the receptor. Barbiturates potentiate GABA-induced increases in chloride conductance and depress voltage-activated calcium currents while prolonging the duration of GABA-induced chloride channel opening. Butalbital may also inhibit the excitatory effects mediated by AMPA receptors by reducing glutamate-induced depolarizations of the receptor. 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. Butalbital is a potentiator of GABA subunits alpha 1 through 6. Some side effects of taking butalbital may include nausea, constipation, tremor, and dry mouth.

Butalbital Pathway References