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Additional information about the drug Baclofen


Baclofen, sold under the brand name Lioresal among others, is a medication used to treat spasticity. It is used as a central nervous system depressant and skeletal muscle relaxant. It is also used in topical creams to help with pain.
Chemically it is a derivative of the neurotransmitter γ-aminobutyric acid (GABA). It is believed to work by activating (or agonizing) GABA receptors, specifically the GABA B receptors.
As of 2015 the cost for a typical course of treatment in the United States is less than 25 USD.
Contents
1 Medical uses
1.1 Spasticity
1.2 Alcoholism
1.3 Others
2 Side effects
2.1 Withdrawal syndrome
2.2 Abuse potential
3 Overdose
4 Pharmacology
4.1 Pharmacodynamics
4.2 Pharmacokinetics
5 Chemistry
6 History
7 Society and culture
7.1 Routes of administration
7.2 Other names
8 References
9 External links
Medical uses
Spasticity
Baclofen is primarily used for the treatment of spastic movement disorders, especially in instances of spinal cord injury, cerebral palsy, and multiple sclerosis.
Alcoholism
Baclofen is being studied for the treatment of alcoholism.
In 2014, the French drug agency ANSM issued a 3-year temporary recommendation allowing the use of baclofen in alcoholism.
Others
It is being studied along with naltrexone and sorbitol for Charcot-Marie-Tooth disease (CMT), a hereditary disease that causes peripheral neuropathy.
Side effects
Briefly, adverse effects may include drowsiness, dizziness, weakness, fatigue, headache, trouble sleeping, nausea and vomiting, urinary retention, or constipation. A complete list of reported adverse effects can be found on the product insert.
Withdrawal syndrome
Discontinuation of baclofen can be associated with a withdrawal syndrome which resembles benzodiazepine withdrawal and alcohol withdrawal. Withdrawal symptoms are more likely if baclofen is used for long periods of time (more than a couple of months) and can occur from low or high doses. The severity of baclofen withdrawal depends on the rate at which it is discontinued. Thus to minimise withdrawal symptoms, the dose should be tapered down slowly when discontinuing baclofen therapy. Abrupt withdrawal is more likely to result in severe withdrawal symptoms. Acute withdrawal symptoms can be stopped by recommencing baclofen.
Withdrawal symptoms may include auditory hallucinations, visual hallucinations, tactile hallucinations, delusions, confusion, agitation, delirium, disorientation, fluctuation of consciousness, insomnia, dizziness (feeling faint), nausea, inattention, memory impairments, perceptual disturbances, pruritus/itching, anxiety, depersonalization, hypertonia, hyperthermia, formal thought disorder, psychosis, mania, mood disturbances, restlessness, and behavioral disturbances, tachycardia, seizures, tremors, autonomic dysfunction, hyperpyrexia (fever), extreme muscle rigidity resembling neuroleptic malignant syndrome and rebound spasticity.
Abuse potential
Russian baclofen (branded Baclosan) 25 mg tablets with a warning reads: “This drug may cause psychomotor retardation ”
Baclofen, at standard dosing, does not produce euphoria or other pleasant effects, does not possess addictive properties, and has not been associated with any degree of drug craving.
Overdose
Reports of overdose indicate that baclofen may cause symptoms including vomiting, weakness, sedation, somnolence, respiratory depression, seizures, unusual pupil size, dizziness,
Pharmacology
Pharmacodynamics
Baclofen produces its effects by activating the GABA B receptor, similar to the drug phenibut which also activates this receptor and shares some of its effects. Baclofen is postulated to block mono-and-polysynaptic reflexes by acting as an inhibitory neurotransmitter, blocking the release of excitatory transmitters. However, baclofen does not have significant affinity for the GHB receptor, and has no known abuse potential. The modulation of the GABA B receptor is what produces baclofen’s range of therapeutic properties.
Similarly to phenibut (β-phenyl-GABA), as well as pregabalin (β-isobutyl-GABA), which are close analogues of baclofen, baclofen (β-(4-chlorophenyl)-GABA) has been found to block α 2 δ subunit -containing voltage-gated calcium channels (VGCCs).
Pharmacokinetics
The drug is rapidly absorbed after oral administration and is widely distributed throughout the body. Biotransformation is low and the drug is predominantly excreted unchanged by the kidneys. The half life of baclofen is roughly 2–4 hours and it therefore needs to be administered frequently throughout the day to control spasticity appropriately.
Chemistry
Baclofen is a white (or off-white) mostly odorless crystalline powder, with a molecular weight of 213.66 g/mol. It is slightly soluble in water, very slightly soluble in methanol, and insoluble in chloroform.
History
Historically, baclofen was designed as a drug for treating epilepsy. It was first made at Ciba-Geigy, by the Swiss chemist Heinrich Keberle, in 1962. Its effect on epilepsy was disappointing, but it was found that in certain people, spasticity decreased.
Currently, baclofen continues to be given by mouth, with variable effects. In severely affected children, the oral dose is so high that side-effects appear, and the treatment loses its benefit. How and when baclofen came to be used in the spinal sac ( intrathecally ) remains unclear, but as of 2012
In his 2008 book, Le Dernier Verre (translated literally as The Last Glass or The End of my Addiction ), French-American cardiologist Olivier Ameisen described how he treated his alcoholism with baclofen. Inspired by this book, an anonymous donor gave $750,000 to the University of Amsterdam in the Netherlands to initiate a clinical trial of high-dose baclofen, which Ameisen had called for since 2004.
Society and culture
Routes of administration
Baclofen 20 mg oral tablet
Baclofen can be administered transdermally as part of a pain-relieving and muscle-relaxing topical cream mix at a compounding pharmacy, orally (directly into the cerebral spinal fluid) using a pump implanted under the skin.
Intrathecal pumps offer much lower doses of baclofen because they are designed to deliver the medication directly to the spinal fluid rather than going through the digestive and blood system first. They are often preferred in spasticity patients such as those with spastic diplegia, as very little of the oral dose actually reaches the spinal fluid. Besides those with spasticity, intrathecal administration is also used in patients with multiple sclerosis who have severe painful spasms which are not controllable by oral baclofen. With pump administration, a test dose is first injected into the spinal fluid to assess the effect, and if successful in relieving spasticity, a chronic intrathecal catheter is inserted from the spine through the abdomen and attached to the pump which is implanted under the abdomen’s skin, usually by the ribcage. The pump is computer-controlled for automatic dosage and the reservoir in the pump can be replenished by percutaneous injection. The pump also has to be replaced about every 5 years due to the battery life and other wear.
Other names
Synonyms include chlorophenibut. Brand names include Beklo, Baclodol, Flexibac, Gablofen, Kemstro, Liofen, Lioresal, Lyflex, Clofen, Muslofen, Bacloren, Baklofen, Sclerofen, and others.

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