Baclofen

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H301：Giftig bei Verschlucken.

Baclofen Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R61:Kann das Kind im Mutterleib schädigen.
  R25:Giftig beim Verschlucken.
  R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
  R42/43:Sensibilisierung durch Einatmen und Hautkontakt möglich.
  R20/21/22:Gesundheitsschädlich beim Einatmen,Verschlucken und Berührung mit der Haut.

• S-Sätze Betriebsanweisung:

  S53:Exposition vermeiden - vor Gebrauch besondere Anweisungen einholen.
  S22:Staub nicht einatmen.
  S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.
  S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).
  S52:Nicht großflächig für Wohn- und Aufenthaltsräume zu verwenden.
  S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.

• Chemische Eigenschaften

  Off-White Solid

• Originator

  Lioresal,Ciba Geigy,Switz.,1971

• Verwenden

  Specific GABA-B receptor agonist. Muscle relaxant (skeletal)

• Verwenden

  (±)-Baclofen has been used as γ-aminobutyric acid receptor B GABA_B?receptor agonist:
  
  • as well as control GABAergic drug to test its protective effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic toxicity
  • to test its effects on in vivo motor function tests and performance of mutant mice
  • to test its excitability effect on dopaminergic (DA) neurons of the ventral tegmental area (VTA)
  • to test its effect in reducing dendritic excitability in Purkinje neurons
  
  

• Verwenden

  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.

• Definition

  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.

• Manufacturing Process

  42.45 g of β-(p-chlorophenyl)glutaric acid imide are stirred into a solution of 8.32 g of sodium hydroxide in 200 ml of water. The mixture is heated for 10 minutes at 50°C, and the solution thus formed is cooled to 10° to 15°C. At this temperature there are then added dropwise a solution of 40.9 g of sodium hydroxide in 200 ml of water and then, in the course of 20 minutes, 38.8 g of bromine. When all has been dropped in, the batch is stirred for 8 hours at 20° to 25°C. The reaction solution is then cautiously adjusted with concentrated hydrochloric acid to pH 7, whereupon finely crystalline γ-amino- β-(p-chlorophenyl)butyric acid settles out. To purify it, it is recrystallized from water. Melting point is 206°to 208°C.

• Trademarks

  Kemstro (Schwarz Pharma); Lioresal (Medtronic); Lioresal (Novartis).

• Therapeutic Function

  Muscle relaxant

• Biologische Funktion

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

• Allgemeine Beschreibung

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

• Air & Water Reaktionen

  Insoluble in water.

• Reaktivität anzeigen

  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.

• Health Hazard

  SYMPTOMS: Symptoms of exposure to Baclofen via ingestion may include drowsiness, insomnia, dizziness, weakness, mental confusion, nausea, constipation, anorexia, urinary retention, impotence, nystagmus, diplopia and incoordination. Ingestion may lead to cholinergic effects and lassitude. It may also lead to ataxia. Other symptoms due to ingestion may include impaired renal function, fatigue, headache, hypotension, urinary frequency, rash, pruritis, ankle edema, excessive perspiration, weight gain, nasal congestion, and rarely, euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, tremor, rigidity, dystonia, blurred vision, strabismus, miosis, mydriasis, dysarthia, epileptic seizure, dyspnea, palpitation, chest pain, syncope, dryness of the mouth, taste disorder, abdominal pain, vomiting, diarrhea, blood in the stools, enuresis, dysuria, inability to ejaculate, nocturia and hematuria. Overexposure through ingestion may result in seizures, and coma with respiratory depression. Aspiration pneumonia is a frequent complication of coma with respiratory depression. Other symptoms due to overdosage may include vomiting, muscular hypotonia, drowsiness, and accommodation disorders. Cyanosis has been reported. Chronic ingestion may result in drowsiness, depression, weakness, anxiety, ataxia, headaches, blurred vision, gastric upset and pruritic skin rashes characterized by urticaria or erythematous macular eruptions. Sudden withdrawal after chronic ingestion may cause auditory and visual hallucinations, anxiety and tachycardia. Seizures may also occur after sudden withdrawal. Abuse may lead to drug dependence.

• Brandgefahr

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

• Biologische Aktivität

  Selective GABA B receptor agonist. Skeletal muscle relaxant.

• Biochem/physiol Actions

  Baclofen, a γ-aminobutyric acid (GABA) analog, possesses myorelaxant properties Being a γ-aminobutyric acid receptor B (GABAB) agonist, baclofen may be involved in the potentiation of dendritic potassium K+?channels. It may be useful in blocking transient lower esophageal sphincter relaxation (TLESR)?in gastroesophageal reflux disease (GERD). Baclofen may also have scope for treating addictive especially, in alcohol use disorder (AUD).

• Mechanism of action

  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.

• Clinical Use

  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.

• Nebenwirkungen

  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.

• Sicherheitsprofil

  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^-

• Synthese

  Baclofen, 4-amino-3-(4-chlorophenyl)butyric acid (15.3.5), is synthesized in two ways. According to the first, 4-chlorobenzaldehyde is condensed with two moles of acetoacetic ester, giving the product (15.3.1), which initially undergoes alkaline hydrolysis and decarboxylation forming 3-(4-chlorphenyl)glutaric acid (15.3.2). Dehydration of this gives 3-(4-chlorophenyl)glutaric acid anhydride (15.3.3), and further treatment with ammonia gives the corresponding glutarimide (15.3.4). Reacting this with an alkaline solution of a halogen (Hofmann rearrangement) gives baclofen (15.3.6).

  

• Veterinary Drugs and Treatments

  Baclofen may be useful to decrease urethral resistance in dogs to treat urinary retention. It is not recommended for cats.

• in vitro

  (±)-baclofen dampened cell growth in human hepatocellular carcinoma (hcc) cells in a dose-dependent manner. (±)-baclofen also caused cell cycle arrest at g0/g1 phase without inducing cell death. additionally, (±)-baclofen-evoked hcc cells proliferation was associated with down-regulation of the intracellular camp level, up-regulation of p21waf1 protein expression and its phosphorylation level, which could be reversed by pretreatment with the gabab antagonist, phaclofen, indicating that (±)-baclofen-evoked growth blockade was exerted in a gabab-dependent fashion [1].

• in vivo

  the mice, subcutaneously injected with bel-7402 cells, were given an intraperitoneal injection of (±)-baclofen 30 mg/kg every day for 30 days. compared with the control, (±)-baclofen remarkably blocked the bel-7402 xenograft tumor growth without causing toxic effects via measuring the relative tumor volume and the mean body weight change in (±)-baclofen-treated groups, which could make (±)-baclofen as an effective and relatively safe potential drug for the treatment of hcc [1].

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Anti-arrhythmics: enhanced muscle relaxant effect with procainamide.
  Antidepressants: enhanced muscle relaxant effect with tricyclics.
  Antihypertensives: enhanced hypotensive effect. Lithium: use with caution.

• IC 50

  200 nm: a selective agonist of γ-aminobutyric acid metabotropic receptor (b) (gabab).

• Stoffwechsel

  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.

• Lager

  Room temperature

• Einzelnachweise

  [1]. wang, t., huang, w., & chen, f. baclofen, a gabab receptor agonist, inhibits human hepatocellular carcinoma cell growth in vitro and in vivo. life sciences. 2008; 82(9-10): 536-541.

Baclofen Upstream-Materialien And Downstream Produkte

Baclofen Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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