Баклофен

Химические свойства

Off-White Solid

Использование

Baclofen may be used as a pharmaceutical secondary reference standard for the determination of the analyte in plasma samples by liquid chromatography tandem mass spectrometry and tablet formulations by UV spectroscopy, respectively.

Определение

ChEBI: A monocarboxylic acid that is butanoic acid substituted by an amino group at position 4 and a 4-chlorophenyl group at position 3. It acts as a central nervous system depressant, GABA agonist and muscle relaxant.

Биологические функции

Baclofen (Lioresal) is the parachlorophenol analogue of the naturally occurring neurotransmitter γ-aminobutyric acid (GABA).

Общее описание

Odorless or practically odorless white to off-white crystalline powder.

Реакции воздуха и воды

Insoluble in water.

Профиль реактивности

Baclofen is an amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.

Пожароопасность

Flash point data for Baclofen are not available. Baclofen is probably combustible.

Биологическая активность

Selective GABA B receptor agonist. Skeletal muscle relaxant.

Механизм действия

Baclofen appears to affect the neuromuscular axis by acting directly on sensory afferents, γ-motor neurons, and collateral neurons in the spinal cord to inhibit both monosynaptic and polysynaptic reflexes. The principal effect is to reduce the release of excitatory neurotransmitters by activation of presynaptic GABAB receptors. This seems to involve a G protein and second-messenger link that either increases K⁺ conductance or decreases Ca⁺⁺ conductance.

Клиническое использование

Baclofen is an agent of choice for treating spinal spasticity and spasticity associated with multiple sclerosis. It is not useful for treating spasticity of supraspinal origin. Doses should be increased gradually to a maximum of 100 to 150 mg per day, divided into four doses.

Побочные эффекты

Side effects are not a major problem, and they can be minimized by graduated dosage increases.They include lassitude, slight nausea, and mental disturbances (in including confusion, euphoria, and depression). The drowsiness is less pronounced than that produced by diazepam—an important therapeutic advantage. Hypotension has been noted, particularly following overdose. Elderly patients and patients with multiple sclerosis may require lower doses and may display increased sensitivity to the central side effects. Baclofen may increase the frequency of seizures in epileptics.

Профиль безопасности

Poison by ingestion,subcutaneous and intravenous routes. Human systemiceffects by ingestion: blood pressure lowering, coma,muscle weakness, pulse rate decrease, respiratorydepression. When heated to decomposition it emits toxicfumes of Cl^-

Метаболизм

Baclofen is rapidly and effectively absorbed after oral administration. It is lipophilic and able to penetrate the blood-brain barrier.Approximately 35% of the drug is excreted unchanged in the urine and feces.