Carisoprodol-350, The Overlooked Muscle Relaxer
Muscle pain affects approximately 1.7 billion people worldwide and is regarded as a major social burden. Musculoskeletal conditions are a common problem in the States and one of the most common causes of disability claims. Low back pain is one of the leading causes of disability in 160 countries and is associated with limited mobility, poor quality of life, and workplace absenteeism. Pain-relief measures in such conditions are crucial for symptomatic relief and maintaining your work life and employment.
Usually, NSAIDs are the first line of treatment among healthcare providers and general practitioners because of their safe nature and efficiency in working on pain caused by slow tissue damage. Other than analgesics, muscle relaxants are equally effective treatment measures that are sadly overlooked because of the stigma of adverse reactions associated with their use. Carisoprodol is a short-term muscle relaxer that is indicated for relief from the discomfort associated with painful musculoskeletal conditions. It has shown highly satisfactory relief from acute painful musculoskeletal conditions like sprains and muscle injuries when coupled with other rest, therapy, and other methods.
A word on Carisoprodol 350
Carisoprodol was introduced for medical use in 1959 and marketed under the trade name Soma. It is closely related to Meprobamate in structure. Still, it has a different pharmacological profile because of the differences in subunit-dependent sites of either drug and their binding locations.
Image credits- https://www.ncbi.nlm.nih.gov/books/NBK553077/#:~:text=Carisoprodol%20indications%20include%20the%20relief,%2C%20sprains%2C%20and%20muscle%20injuries.
Most muscle relaxants work on two primary conditions of muscle affection, i.e., spasticity and spasm. Spasticity is a long-term muscle inflammation that, along with causing pain and discomfort and affects a person’s speech and movement. Spasms, in comparison, are localized rashes that occur when the muscles are overused during intense training sessions.
Based on the muscle contractions, muscle relaxants are either Antispastics or Antispasmodic. Antispastics work on the neurotransmission in the brain to work for upper motor syndromes like brain injury and stroke patients. Antispasmodics work on the smooth muscles to prevent muscle cramps and spasms. Pilot studies regarding Carisoprodol have observed its antispasmodic effects on muscle cramps experienced by people with neurological, vascular, and arthritic diseases and achieved an efficacy of 81% in relieving the symptoms. To carry out its muscle-relaxant effects, Carisoprodol binds to the GABA receptors presynaptically and postsynaptically to inhibit spinal reflexes while inhibiting substance P release into the spinal cord to reduce pain.
Studies have shown patients with acute muscle spasms of the lower back to have significantly greater and more rapid relief from starting backache with an improved functional status during treatment with carisoprodol 350-mg tablets compared to placebo.
Is Carisoprodol a barbiturate
It is known that barbiturates bind to both open and closed states of the Acetylcholine receptors and block the flow of ions through the channel to induce their sedative, muscle-relaxant, and anti-convulsive effects. Carisoprodol allosterically modulates and directly activates human alpha1 beta2 gamma2 GABA(A)R function in a barbiturate-like manner without the adverse reactions induced by the use of barbiturates. . In the absence of GABA, Carisoprodol produces picrotoxin-sensitive, inward currents that were significantly larger than those produced by Meprobamate; a factor that reduces the risk of seizures with and gives it a neurological advantage,
Both Carisoprodol and Meprobamate are considered barbiturates because of similar effects on the GABA receptors of the brain. But in reality, it is a muscle relaxant that interrupts the neuronal communication within the reticular formation and spinal cord to ease the muscular pain.
In a double-blind study conducted to determine Carisoprodol effectiveness and to test whether it produced a more significant effect than an active sedative control, Forty-eight migrant farm laborers with acute lumbar strain and spasm were administered Carisoprodol 350mg, Butabarbital 15 mg or placebo four times daily for four days. During this period, the degree of limitation of motion was recorded and compared with the improvement in the final results.
Among the forty-eight subjects, forty-three showed significantly more effectiveness than butabarbital and placebo in reducing pain symptoms. The study showed that Carisoprodol exerts an intrinsic muscle-relaxant activity and is not solely dependent on its sedative action to carry out its function.
What about the addiction potential of Carisoprodol
In a study conducted to evaluate the addiction potential of Carisoprodol with its withdrawal effects, the subjects were exposed to a placebo for 12 days and Carisoprodol for approximately 18 days, after which the drug was withdrawn abruptly replaced by identical appearing capsules. While observations were made three times daily throughout the experiment, toxicity was evaluated through observations and laboratory tests. None of the clinical statements or laboratory tests showed significant deviations from pre-drug observations.
Following Carisoprodol withdrawal, none of the subjects realized that their medication had been changed or showed signs of abstinence. ECG patterns, in comparison, showed a mild change that was further elevated on using the drug for more than 18 days. None of the patients observed paroxysmal changes in the form of dizziness, swaying sensations, seizures, or collapses during the withdrawal period as followed with barbiturates, nor did the clinical observations or lab-test show significant deviation from pre-drug comments.
The study showed that chronic administration of Carisoprodol did not induce a barbiturate intoxication pattern and impact the person’s mental, emotional, or judgment capacity. No symptoms of barbiturate-like abstinence in the form of anxiety, fine tremor, weakness, convulsions, and delirium were observed on abruptly discontinuing its use.
But there still is the possibility of intoxication when used continuously in large doses and a meprobamate type of abstinence when abruptly withdrawn because of Carisoprodol’s relationship with the Meprobamate. Considering the factors mentioned above, Carisoprodol should be used in regulated doses for a short term and discontinued in tapering strengths.
Can Carisoprodol be in breastfeeding mothers?
Breastfeeding women are at an increased risk of muscle pain because of prolonged hours of holding the infant and trying feeding positions coupled with poor feeding positions and fatigue or stress factors that aggravate the problem. A risk of medications during this time is they can pass into the breast milk and harm the infant, a factor that puts Cariprodol at an advantage because of its safety conditions.
In a study conducted to evaluate the drug’s safety, concentrations of Carisoprodol and Meprobamate were measured in the breast milk of subjects using Carisoprodol in strengths of 2100 mg/ day. The average milk concentrations were 0.9 microg/mL for Carisoprodol and 11.6 microns/mL for Meprobamate. Based on the milk concentrations measured, the absolute dose ingested by an exclusively breastfed infant could be estimated at 1.9 mg/kg per day, and the relative quantity would be 4.1% of the weight-adjusted maternal dose. No adverse effects were observed in the infant, but the infant was partly fed with formula because of insufficient maternal milk production.
The study, coupled with other available data, has led researchers to conclude that Carisoprodol can be used for a short duration in breastfeeding mothers if needed. Still, the infant should be put off breast milk and formula fed during that time.
Conclusion
While some antispasmodics may treat spasticity in addition to spasms, their use should not be conducted for longer periods as it can lead to intoxication and addiction complications. Carisoprodol is recommended to relieve discomfort and pain in acute musculoskeletal conditions, and it is not indicated to treat spasticity and should be avoided in such cases. When administered three times daily and at bedtime, carisoprodol 250 mg is as effective as 350 mg daily and at rest, with a lower incidence of adverse events and fewer discontinuations of therapy due to adverse events. The safety and efficacy of Carisoprodol have not been established in patients under the age of 16 or over the age of 65 because of which it should not be used in younger and elderly patients.
https://pubmed.ncbi.nlm.nih.gov/22094194/
https://www.ncbi.nlm.nih.gov/books/NBK553077/
https://www.sciencedirect.com/topics/neuroscience/carisoprodol
https://pubmed.ncbi.nlm.nih.gov/4262210/
https://pubmed.ncbi.nlm.nih.gov/19908948/
https://agsjournals.onlinelibrary.wiley.com/doi/abs/10.1111/j.1532-5415.1963.tb00340.x
