Introduction to Baclofen

Baclofen, which is also known as Lioresal, Baclon, Kemstro, 4-Amino-3-(4-chlorophenyl)butanoic acid, Lioresal Intrathecal, Pms-Baclofen, 1134-47-0, DL-Baclofen, is s a white to off-white, practically odorless crystalline powder that is slightly soluble in water or in methanol, and insoluble in chloroform. The substance is considered useful in alleviating symptoms of spasticity due to multiple sclerosis. It is also helpful in treating patients with spinal cord injuries. In France, baclofen has been approved for use in the treatment of alcoholism through the French Agency for the Safety of Health Products, The Agence française de sécurité sanitaire des produits de santé.

It is not, however, indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders, or in treating stroke, cerebral palsy or Parkinson’s disease. The drug is dispensed in tight, child-resistant containers of 100-500 pills per bottle. It is suggested the pills be stored at 15°-30°C (59°-86°F).

Using Baclofen

Ways of Administration

• Orally
• By Intrathecal pump

Optimal oral dosage requires individual titration and is best started at low mg and increased in 5 mg amounts over three day periods, for example 10 mg for three days, then graduating to 15 mg three days later and so on, till the proper dose for a patient is determined.

Effects of Baclofen

Positive: Relaxation of muscles

Negative: See side effects below

Combinations with Baclofen

Often combined with over-the-counter pain medications, anti-depressants (MAOI's SSRI's, SNRI's, TCA's), which can cause additional muscle weakness when combined, and/or with anti-inflammatory medications. Extra care should be taken when combined with sleeping medications or opiate/opioid drugs.

Further, baclofen depresses the central nervous system. When combined with monoamine oxidase inhibitors (phenelzine [Nardil], tranylcypromine or [Parnate] greater depression of brain function as well as low blood pressure can result. Baclofen can also increase blood sugar, thus making doses of antidiabetic drug adjustments when baclofen is added.

Different Uses for Baclofen

Muscle rigidity, multiple sclerosis and treatment for some forms of spinal cord damage. It is also used as a treatment to help alcoholics quit drinking and to stay sober.

Pharmacology of Baclofen

Baclofen inhibits monosynaptic and polysynaptic reflexes at the spinal level, possibly by hyperpolarization of afferent terminals. It is an analog of the putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA), yet there is no conclusive evidence to support that it effects on the GABA systems involve clinical effects. Baclofen is rapidly and extensively absorbed and eliminated. Absorption may be dose-dependent, being reduced with increasing doses. To date, the exact mechanism of baclofen are not fully known.

Chemistry of Baclofen

Column 1
Systematic(IUPAC) name:(RS)-4-amino-3-(4-chlorophenyl)butanoic acid
Synonyms: (3R)-4-Amino-3-(4-chlorophenyl)butanoic acid [ACD/IUPAC Name]; (3R)-4-Amino-3-(4-chlorophenyl)butyric acid; (3R)-4-Amino-3-(4-chlorphenyl)butansäure [German] [ACD/IUPAC Name]; (R)-(-)-4-Amino-3-(4-chlorophenyl)butanoic acid; (R)-(-)-4-Amino-3-(4-chlorophenyl)butyric acid; (R)-(-)-Baclofen; (R)-4-Amino-3-(4-chlorophenyl)butanoic acid; (R)-Baclofen; (βR)-β-(Aminomethyl)-4-chlorobenzenepropanoic acid; Acide (3R)-4-amino-3-(4-chlorophényl)butanoïque [French] [ACD/IUPAC Name]
Molecular Formula: C10H12ClNO2
Molar mass: 213.055649 Da
CAS Registry Number: 1134-47-0
Melting Point: 206-208 oC
Boiling Point: 364.3 °C at 760 mmHg; (10)Vapour Pressure: 6.01E-06 mmHg at 25°C.
Flash Point: 174.1 °C; (8)Enthalpy of Vaporization: 64.41 kJ/mol; (9)
Solubility: Soluble in water (pH 7.6) (4.3 mg/ml), dilute aqueous acid (> 20 mg/ml), dilute aqueous base (>20 mg/ml), ethanol (0.02 mg/ml), and methanol (slightly soluble). Insoluble in acetone, chloroform, and ether.

The Dangers of Baclofen

Physical Health Risks

It has been noted that hallucinations and seizures can be a side effect of abrupt withdrawal from baclofen along with muscle stiffness, high fever, confusion, changes in mental status, multiple organ failure, and ultimately, in some rare cases, death. It is therefore noted that except when the drug causes allergic reactions or serious adverse conditions, the medication should be reduced slowly rather than discontinue the drug completely at one time.

Baclofen is not advised in pregnant women or children under the age of 12, and should be used with extreme caution in those with epilepsy. Driving while under the influence of baclofen until the patient fully evaluates their reaction to the medication, which often causes sleepiness. Alcohol should be avoided completely while taking this central nervous system depressant.

Overdose

Signs of overdose include vomiting, muscular hypotonia, drowsiness, accommodation disorders, coma, respiratory depression and seizures. Patients in a state of consciousness are encouraged to try to induce vomiting after an overdose, and those who are not conscious should instead be rushed to the nearest emergency room without attempting to induce vomiting, as the chances for choking on vomit increase heavily with an unconscious individual.

Reported Deaths

Baclofen has been known to cause death in people who have taken extremely large doses and mixed with alcohol or other drugs: http://cicm.org.au/journal/2000/september/Case2.pdf Also in rare circumstances, when the drug has been stopped suddenly, seizure and ultimate death has occurred, though rarely.

Mental Health Risks

In rare cases, sudden stopping of the drug has been noted to cause mental confusion.

Side Effects

In controlled studies, 63% of patients receiving baclofen noticed tiredness and/or weakness and fatigue, with under 12% noting headache (4-8%), insomnia (2-7%); and, rarely, euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, coordination disorder, tremor, rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis, mydriasis, diplopia, dysarthria, epileptic seizure. Rare instances of Hypotension (0-9%).

Rare instances of dyspnea, palpitation, chest pain, syncope were further noted, with nausea (4-12%), constipation (2-6%); anddry mouth, anorexia, taste disorder, abdominal pain, vomiting, diarrhea, and positive test for occult blood in stool, urinary frequency (2-6%), enuresis, urinary retention, dysuria, impotence, inability to ejaculate, nocturia, hematuria rarely noted, along with a few instances of rash, pruritus, ankle edema, excessive perspiration, weight gain, nasal congestion. Also noted was that most symptoms related to central nervous and genitourinary symptoms may be related to the underlying disease rather than to drug therapy.

Addiction

Physical Addiction

Not thought to be physically addictive, although tapering rather than stopping cold turkey is always suggested with this drug.

Mental Addiction

According to a study done by Jamous A, Kennedy P, Psychol C, Grey N. in 1994, no major adverse psychological effects were noted.--pubmed.com

Producing/Growing Baclofen

Forms of Baclofen

• Oral
• Intrathecal

Legal Status of Baclofen

United Nations

By prescription

USA

By prescribtion

EU

By prescription

Other Countries

History of Baclofen

Baclofen was first synthesized by Ciba-Geigy's Swiss chemist Heinrich Keberle in 1962. After initial disappointing results in the drug's first intended use for treatment of epilepsy, it was then used successfully in treating muscle spasticity. The French government also considers it successful in treating alcoholism since 2009, though conflicting research has left many other governments not agreeing with its use in treating alcoholism, including the U.S.'s FDA, who has yet to approve baclofen for treating alcoholism.

More Baclofen Sections

Baclofen

References

http://pubchem.ncbi.nlm.nih.gov/summ...=2284#itabs-2d
http://www.webmd.com/drugs/drug-8615...px?drugid=8615
Jamous A, Kennedy P, Psychol C, Grey N.