Pathways

Busulfan is an antineoplastic from the alkylating agent drug class. Although, its structure is not an analog of the nitrogen mustard drug. This drug is indicated as a combination with cyclophosphamide for a regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia. Busulfan can also be used as a component of a pretransplant conditioning agent before bone marrow transplantation for acute myeloid leukemia and nonmalignant disease. This drug is cell cycle-nonspecific and works by three different mechanisms. Those all lead to the disruption of the DNA and the apoptosis of the cell. Busulfan contains two labile methanesulfonate groups. After the hydrolyzation of the molecule, the methanesulfonate groups are released and carbonium ions are produced. These carbonium ions alkylate DNA, mostly the guanine bases. This leads to the inhibition of DNA replication and RNA transcription. Specifically, busulfan creates intrastrand crosslinks between guanine and adenine bases. Those damages cannot be repaired by the cellular machinery. This drug is administered as an intravenous injection or as an oral tablet.

Busulfan is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Busulfan passes through the liver and is then excreted from the body mainly through the kidney.

Butabarbital is a barbiturate drug used as a sedative and hypnotic. Butabarbital, or Butisol, is a fast onset barbiturate with short duration of action compared to other barbiturates. This makes butabarbital a useful drug for treating severe insomnia and pre-operative anxiety. Barbiturates like butabarbital potentiate GABA-A receptors and inhibit receptors. GABA-A receptors are predominantly on the post-synaptic membrane, and upon activation, open chloride channels to hyperpolarize the neuron and decreased firing rate. Potentiation of GABAergic neurons produces sedation. Butabarbital binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane.

Butabarbital is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Butabarbital passes through the liver and is then excreted from the body mainly through the kidney.

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.

Metabolites of Butalbital are predicted with biotransformer.