Baclofen

Baclofen is primarily used for the treatment of spastic movement disorders, especially in instances of spinal cord injury, and multiple sclerosis. Use in people with stroke, cerebral palsy, or Parkinson's disease is not recommended. Baclofen is also indicated as a treatment for alcohol use disorder in which it is effective in reducing the risk of relapse, and to increase the number of days that a person can go without drinking alcohol (abstinence days), though this indication remains off-label in many countries It is sometimes used off-label for the treatment of opioid withdrawal symptoms, and may be superior for this purpose to the more-commonly used clonidine. It increases slow-wave sleep. ==Adverse effects==

Adverse effects include drowsiness, dizziness, weakness, fatigue, headache, trouble sleeping, nausea and vomiting, poor concentration and recall (resembling dementia), urinary retention, or constipation. Withdrawal symptoms may include auditory hallucinations, visual hallucinations, tactile hallucinations, delusions, confusion, agitation, delirium, disorientation, fluctuation of consciousness, insomnia, dizziness, nausea, inattention, memory impairments, perceptual disturbances, itching, anxiety, depersonalization, hypertonia, hyperthermia (higher than normal temperature without infection), 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==

" Baclofen can produce a feeling of well-being, relaxation, and mild euphoria. Baclofen, at standard dosing, does not appear to possess addictive properties, and has not been associated with any degree of drug craving. Some individuals report feeling high or euphoric at higher doses, often leading to potential abuse. Euphoria is however listed as a common to very common side effect of baclofen in the BNF 75. There are very few cases of abuse of baclofen for reasons other than attempted suicide. These effects are likely mediated not by activation of the GABAB receptor, but rather by activation of the GHB receptor. It acts on GABA receptors to inhibit nerve activity, which produces a calming effect. Baclofen possesses both sedative and anxiolytic properties. ==Overdose==

Reports of overdose indicate that baclofen may cause symptoms including vomiting, general weakness, sedation, respiratory insufficiency, seizures, dizziness, headaches, Overdose may require intubation and length of mechanical ventilation required may correlate with serum baclofen levels shortly after ingestion. Symptoms may persist even after the point at which serum baclofen levels are undetectable. ==Pharmacology==

Chemically, baclofen is part of a class of compounds that are called Gabapentinoids. Those compounds are all derivatives of the neurotransmitter γ-Aminobutyric acid (GABA). Baclofen is believed to work by activating (or agonizing) GABA receptors, specifically the GABAB receptors. Pharmacodynamics Baclofen produces its effects by selectively activating the GABAB receptor. Baclofen is postulated to block mono-and-polysynaptic reflexes by acting as an inhibitory ligand, inhibiting the release of excitatory neurotransmitters. Baclofen does not have significant affinity for the GHB receptor, and has no known abuse potential. Agonism of GABAB receptors is thought to be responsible for baclofen's range of therapeutic properties, as GABAB knockout mice are unresponsive to the neurobiological effects of baclofen. Similarly to other Gabapentinoids like Phenibut (β-phenyl-GABA), as well as Pregabalin (β-isobutyl-GABA) and Gabapentin (3-cyclohexyl-GABA), Baclofen (β-(4-chlorophenyl)-GABA) has been found to block α2δ subunit-containing voltage-gated calcium channels (VGCCs). However, it is weaker relative to phenibut in this action (Ki = 23 and 39 μM for R- and S-phenibut and 156 μM for baclofen). 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. It is classified as a Gabapentinoid medication. ==History==

Historically, baclofen was designed as a drug for treating epilepsy. It was first synthesized at Ciba-Geigy by the Swiss chemist Heinrich Keberle in 1962. Its effect on epilepsy was ineffective, but it was found that in certain people, spasticity decreased. In 1971, it was introduced as a treatment for certain form of spasticity. It was approved by the US Food and Drug Administration (FDA) in 1977. Intrathecal baclofen was first introduced in 1984 to treat severe spinal spasticity. This administration route aimed to avoid supraspinal side effects. ==Society and culture==

Routes of administration Baclofen can be administered, orally, intrathecally (directly into the cerebral spinal fluid) using a pump implanted under the skin, or transdermally as part of a pain-relieving and muscle-relaxing topical cream mix (also containing gabapentin and clonidine) prepared at a compounding pharmacy. Besides those with spasticity, intrathecal administration is also used in patients with cerebral palsy Other names Other names include: Baclosan, Fleqsuvy, Gablofen, Kemstro, Lioresal, Lyvispah, Ozobax. ==Research==

Baclofen is being studied for the treatment of alcoholism. Evidence as of 2019 is not conclusive enough to recommend its use for this purpose. In 2014, the French drug agency ANSM issued a three-year temporary recommendation allowing the use of baclofen in alcoholism. In 2018, baclofen received a Marketing Authorization for use in alcoholism treatment from the agency if all other treatments are not effective. It is being studied along with naltrexone and sorbitol for Charcot–Marie–Tooth disease (CMT), a hereditary disease that causes peripheral neuropathy. It is also being studied for cocaine addiction. Baclofen and other muscle relaxants are being studied for potential use for persistent hiccups. From 2014 to 2017, baclofen misuse, toxicity and use in suicide attempts among adults in the US increased. 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. The researchers concluded, "In summary, the current study did not find evidence of a positive effect of either low or high doses of baclofen in AD patients. However, we cannot exclude the possibility that baclofen is an effective medication for the treatment of severe, heavy drinking AD patients not responding to or not accepting routine psychosocial interventions." == See also ==