Baclofen

213.66

213.66

214-486-9

755906|329137

2811

DTXSID5022641

M03BX01|M - Musculo-skeletal system

2922492050

63.3

-1

white to very faintly yellow solid

1.2069 (rough estimate)

206-208 °C

364.3±32.0 °C(Predicted)

174.1±25.1 °C

1.5500 (estimate)

soluble in dilute NaOH or dilute HCl. soluble in water at approximately 4mg/ml at pH 7.6;1 M HCl: 50 mg/mL

2-8°C

Oral-rat LD50; 145 mg/kg; Oral-Mouse LD50: 200 mg/kg

Flammable; burning produces toxic nitrogen oxides and chloride fumes; patients taking side effects: low blood pressure, reduced pulse, muscle weakness

9.62+ 0.1 (amino group) and 3.87 + 0.1 (carboxyl group)

9.62 + 0.1 (amino group) and 3.87 + 0.1 (carboxyl group)

149.2 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

Insoluble in water.

Acids, Carboxylic

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.

III

6.1(b)

UN 2811 6.1/PG 3

3

61-25-36/37/38-42/43-20/21/22

53-22-36/37/39-45-52-36-26

MW5084200

T,Xn

Ventilated, low temperature and dry; stored separately from food materials in warehouse

Missing Phrase - N15.00950417-P201-P261-P280-P284-P308 + P313

H301-H315-H317-H319-H334-H335-H360

Flash point data for this chemical are not available. It is probably combustible. (NTP, 1992)

|Danger|H301 (91.53%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P272, P280, P281, P285, P301+P310, P302+P352, P304+P340, P304+P341, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P333+P313, P337+P313, P342+P311, P362, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 59 companies from 10 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Fires involving this material can be controlled with a dry chemical, carbon dioxide or Halon extinguisher. (NTP, 1992)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

SMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with water, then transfer the dampened material to a suitable container. Use absorbent paper dampened with water to pick up any remaining material. Seal your contaminated clothing and the absorbent paper in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned. STORAGE PRECAUTIONS: You should store this material in a refrigerator. (NTP, 1992)

RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)

highly

LD50 after oral administration in rats: 145 mg/kg [MSDS] **Overdosage**: Vomiting, muscular hypotonia, drowsiness, accommodation disorders, coma, respiratory depression, and seizures may occur with overdosage. **Pregnancy**: This drug is a pregnancy category C drug. There are no adequate and well-controlled studies that have been performed with pregnant women. Baclofen should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. **Excretion in breastmilk**: It is unknown whether this drug is excreted in human breast milk. Because many drugs are excreted in human milk, caution is warranted when baclofen is administered to a nursing woman.

Limited data are available on the potential hepatotoxicity of baclofen. Among the many clinical trials evaluating the safety and efficacy of baclofen, none mentioned hepatic toxicity or rates of serum ALT elevations occurring during chronic therapy. The product insert starts that 5% of treated patients develop mild serum aminotransferase elevations, but little documentation is available on the significance, severity or duration of these abnormalities. A single case of mild and self-limited hepatitis attirbuted to baclofen has been published. The latency to onset was 3 months, the pattern of injury was hepatocellular, and recovery was rapid and complete, all laboratory tests being normal within a few weeks of stopping.

30%

Baclofen is administered for the relief of signs and symptoms of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and associated pain and clonus, in addition to muscular rigidity. Patients receiving this drug should have reversible spasticity for baclofen to promote the restoration of residual function. This drug is not indicated in the treatment of skeletal muscle spasm caused by rheumatic disorders. The efficacy of baclofen in stroke, cerebral palsy, and Parkinson's disease has not been determined and, therefore, baclofen is not recommended for these conditions.|FDA Label|Treatment of alcohol dependence

Baclofen is a centrally acting muscle relaxant commonly prescribed for spasticity in patients with multiple sclerosis. Baclofen has not been linked to rare instances of mild, self-limited, clinically apparent liver injury.

Autonomic Agents: Muscle Relaxants, Central

In neurological diseases associated with spasm of the skeletal muscles, the clinical effects of baclofen occur due to baclofen action on reflex muscle contractions and of significant relief from painful spasm, automatism, as well as clonus. Baclofen, when used as indicated, improves mobility, increasing levels of independence, and facilitates both passive and active physiotherapy. Baclofen also stimulates gastric acid secretion. GABA-B receptor activation by baclofen may produce protective neurological effects. Baclofen also possesses anti-inflammatory properties that may be of interest in the study of addiction treatment. Preclinical studies have shown that GABA-B receptors have roles in memory storage and retrieval, reward, motivation, mood, as well as anxiety. Neuroimaging studies in humans indicate that baclofen produces region-specific alterations in brain activity.

Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS. (See all compounds classified as GABA-B Receptor Agonists.)|A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358) (See all compounds classified as Muscle Relaxants, Central.)

Rapidly and almost completely absorbed from the gastrointestinal tract. Absorption may be dose-dependent, being reduced with increased doses. Baclofen, when introduced directly into the intrathecal space, allows for effective CSF concentrations to be achieved with resulting plasma concentrations 100 times less than concentrations occurring with oral administration,.|Baclofen is rapidly and extensively eliminated from the body. There is significant intersubject variation in elimination rates. Baclofen is excreted mainly by the kidney as unchanged drug. Seventy to eighty (70 - 80%) of a dose is measured in the urine as unchanged drug. The remainder of the dose is excreted as unchanged drug in the feces or as metabolites in the urine and feces. Excretion is complete within 72 hours after administration.|**Apparent volume of distribution**: 59 liters. Baclofen does not readily cross the blood-brain barrier.|**Total systemic clearance**: 180 mL/min **Renal clearance**: 103 mL/min Baclofen is primarily excreted unchanged by the kidneys. It should be administered cautiously, and it may be necessary to reduce the dosage in patients with reduced renal function.

Approximately 15% of the dose is metabolized in the liver, mainly by deamination. In a clinical study with radiolabeled baclofen, approximately 85% of the dose was excreted unchanged in the urine and feces. The γ-hydroxy metabolite, 3-(p-chlorophenyl)-4-hydroxybutyric acid, is formed by the deamination of baclofen. Because baclofen is partially metabolized in the liver, patients with impaired liver function should be regularly monitored with liver function tests.

Elimination half-life: Approximately 5.5 hours.

The exact mechanism of action of baclofen is not fully understood at this time,. Many studies indicate that baclofen is a GABA-B receptor agonist,,,,. Despite this, there is no conclusive evidence that the effects of baclofen on GABA systems are involved in the production of its clinical effects. Baclofen is an effective and widely used antispastic agent with a spinal site of action. Its mechanism of action and pharmacological properties are different from the effects of other antispastic agents. In addition, baclofen has central sites of action, shown by its adverse event profile and general CNS depressant properties. GABA-B receptors interact with signal transduction pathways and neurotransmitter systems. Baclofen exerts an antinociceptive effect. The clinical significance of this warrants further research data for clarification. Baclofen depresses monosynaptic and polysynaptic reflex transmission, by various actions, and possibly including the stimulation of GABAβ-receptors. This stimulation results in the inhibition of excitatory neurotransmitter (glutamate and aspartate) release, which may normally contribute to pain and spasticity. Although baclofen is an analog of the inhibitory neurotransmitter gamma-amino-butyric acid (GABA), there are no conclusive data indicating GABA systems are involved in its clinical effects.

SYMPTOMS: Symptoms of exposure to this compound 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. (NTP, 1992)

EYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop. SKIN: IMMEDIATELY flood affected skin with water while removing and isolating all contaminated clothing. Gently wash all affected skin areas thoroughly with soap and water. If symptoms such as redness or irritation develop, IMMEDIATELY call a physician and be prepared to transport the victim to a hospital for treatment. INHALATION: IMMEDIATELY leave the contaminated area; take deep breaths of fresh air. If symptoms (such as wheezing, coughing, shortness of breath, or burning in the mouth, throat, or chest) develop, call a physician and be prepared to transport the victim to a hospital. Provide proper respiratory protection to rescuers entering an unknown atmosphere. Whenever possible, Self-Contained Breathing Apparatus (SCBA) should be used; if not available, use a level of protection greater than or equal to that advised under Protective Clothing. INGESTION: DO NOT INDUCE VOMITING. If the victim is conscious and not convulsing, give 1 or 2 glasses of water to dilute the chemical and IMMEDIATELY call a hospital or poison control center. Be prepared to transport the victim to a hospital if advised by a physician. If the victim is convulsing or unconscious, do not give anything by mouth, ensure that the victim's airway is open and lay the victim on his/her side with the head lower than the body. DO NOT INDUCE VOMITING. IMMEDIATELY transport the victim to a hospital. (NTP, 1992)

Apo Baclofen

Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals