Application of a new analgesic Katadolon (flupirtine) in clinical practice

Katadolon - description and action

Katadolon - tablets with analgesic effect

, belong to the group of non-narcotic drugs.
The drug contains 100 mg of the active substance - flupirtine (in the form of flupirtine maleate). A stronger drug with 400 mg of flupirtine is also available, which can be found in pharmacies under the name Katadolon Forte. Additional ingredients include:

• titanium dioxide;
• gelatin;
• magnesium stearate, etc.

The medicine is sold in blisters of 7, 10, 14 tablets or capsules, in packs of 1-5 blisters. Price for 10 capsules

medicines - about 530 rubles. Inside there is a substance of yellow, green color, in capsules - in the form of a powder.

The main indications for the use of Katadolon are determined by the mechanism of its work. It is a selective activator of neuronal potassium channels and is a non-opioid analgesic with central action. The medicine does not lead to the formation of tolerance in the patient’s body and does not bind to opioid, serotonin and other receptors. Its main actions are:

• relaxes muscle tissue (muscle relaxant);
• protecting nerve cells from damage (neuroprotective);
• modulating the mechanism of pain development through a central effect on neurons (painkiller).

After administration, the drug helps suppress the excitation of nerve cells in response to pain, resulting in an analgesic effect. Subsequently, the body's response in the form of pain becomes less intense, and it does not turn into a recurrent form. At the same time, muscle tension is relieved, which also helps relieve pain.

Flupirtine

Flupirtine is a representative of drugs “selective activators of neuronal potassium channels” (“Selective Neuronal Potassium Channel Opener” - SNEPCO) and is a non-narcotic analgesic of central action that does not cause addiction or dependence.

Flupirtine activates G protein-coupled neuronal inward rectifying potassium channels. The release of potassium ions causes stabilization of the resting potential and a decrease in the excitability of neuronal membranes. The result is indirect inhibition of NMDA receptors (N-methyl-D-aspartate), since the blockade of NMDA receptors by magnesium ions persists until depolarization of the cell membrane occurs (indirect antagonistic effect on NMDA receptors).

At therapeutically significant concentrations, flupirtine does not bind to alpha1-, alpha2-receptors, 5HT1-(5-hydroxytrypgophan)-, 5HT2-serotonin, dopamine, benzodiazepine, opioid, central M- and H-cholinergic receptors.

This central action of flupirtine leads to three main effects.

Analgesic effect

Due to the selective opening of voltage-independent potassium channels of neurons with the concomitant release of potassium ions, the resting potential of the neuron is stabilized. The neuron becomes less excitable.

Flupirtine's indirect antagonism of NMDA receptors protects neurons from calcium ion entry. Thus, the sensitizing effect of increasing the intracellular concentration of calcium ions is mitigated. Consequently, when the neuron is excited, the transmission of ascending nociceptive impulses is inhibited.

Muscle relaxant effect

The pharmacological effects described for the analgesic effect are functionally supported by an increase in the uptake of calcium ions by mitochondria, which occurs at therapeutically significant concentrations. Inhibition of impulse transmission to motor neurons and corresponding effects on interneurons lead to a decrease in muscle tension. Thus, this effect occurs mainly in relation to local muscle spasms, and not in relation to the entire muscle as a whole.

Effect on chronization processes

Chronization processes should be considered as processes of neuronal conduction due to the plasticity of neuronal functions. Through the induction of intracellular processes, the plasticity of neuronal functions creates conditions for the implementation of “inflating” type mechanisms, in which the response to each subsequent impulse is strengthened. NMDA receptors (gene expression) are largely responsible for triggering such changes. Indirect blockade of these receptors by flupirtine counteracts the sensation of increased pain. Stabilization of the membrane potential alters the process and thus reduces sensitivity to pain, creating unfavorable conditions for clinically significant chronic pain.

If the pain is already chronic, stabilization of the membrane potential facilitates the “erasing” of pain memory and, thus, reduces sensitivity to pain.

Indications of the drug

Why is Katadolon prescribed? The indications for use are extensive, but it is strictly forbidden to use such a remedy without a doctor’s recommendation! The drug is prescribed for acute or chronic pain, which has varying severity and is provoked by various pathologies of the body.

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Most often, Katadolon is prescribed for pathologies of the musculoskeletal system. These include arthrosis and arthritis accompanied by pain.

Various musculoskeletal pains also disappear during treatment with the drug, especially if they are caused by muscle spasms against the background of damage to the vertebrae and joints.

The medicine has proven itself to be effective for headaches of various origins, as well as for fibromyalgia.

For oncological diseases that are accompanied by pain, a course of medication is recommended. It is prescribed even for moderate manifestations of pain - this allows you to reduce the use of stronger drugs. Other indications for therapy may include:

• pain from injuries, after operations;
• severe pain during menstruation - algomenorrhea;
• severe toothache, unpleasant consequences of tooth extraction.

Katadolon can eliminate the phenomena of painful shock, so it is often used in hospitals.

The problem of pain occupies one of the leading places in modern medicine and is the subject of multidisciplinary research. Currently, it is experiencing a period of intensive study, characterized by the extremely rapid emergence of new studies, concepts, and theories, which sometimes do not have time to receive proper semantic assessment, both in fundamental and practical terms.

Pain is not only a symptom of most diseases, but also a psychophysiological phenomenon involving the mechanisms of regulation and formation of emotions, motor, autonomic and humoral reactions. The occurrence of pain is caused by the complex interaction of peripheral and central neurophysiological mechanisms of convergence, summation, and the ratio of nociceptive and antinociceptive afferent signals at various levels of the central nervous system.

The primary central substrate of the complex interaction of nociceptive and antinociceptive systems is the dorsal horn of the spinal cord. It is here that interaction occurs between the channels of pain and non-pain sensitivity, on the basis of which a flow of ascending impulses of a new quality arises. It is now generally accepted that the transmission of nociceptive signals can primarily change at the level of the spinal cord.

At the segmental level, the implementation of descending influences of the antinociceptive systems of the central nervous system is realized, modulating the formation of a nociceptive flow of impulses to effector neurons of various functional purposes and, ultimately, determining the severity of the body's response to pain at the level of psycho-emotional, motor and autonomic indicators [6].

Under normal conditions, there is a harmonious relationship between the nociceptive and antinociceptive systems, which is disrupted either due to additional activation of the nociceptive system or insufficient function of the antinociceptive system. These relationships can change depending on the nature and depth of tissue damage, acquiring the possibility of their separation in terms of temporal characteristics. Acute pain is a necessary biological adaptive signal about possible (in the case of painful experience), beginning or already occurring damage. The development of acute pain is associated, as a rule, with well-defined painful irritations of superficial or deep tissues and internal organs or dysfunction of the smooth muscles of internal organs without tissue damage. In contrast, chronic pain is a condition that almost always requires medical attention and is characterized by the possibility of a sensation of pain that continues after a period of healing of the damaged tissue.

If acute pain is always a symptom, then chronic pain can become almost an independent disease. It is clear that adequate treatment of acute pain can prevent its chronicization.

The temporary transformation of pain is based on certain pathophysiological mechanisms. From the point of view of the sequence and depth of these changes, nociceptive, neuropathic and psychogenic pain are distinguished. There is reason to believe that the formation of types of pain that reach the psychogenic variant sequentially goes through the listed stages, the duration and depth of which vary significantly in each specific case.

The general principles of pain syndrome therapy include identifying and eliminating the source or cause that caused the pain, determining the degree of involvement of various parts of the nervous system in the formation of pain, and relieving or suppressing the pain itself. For this purpose, a clinical assessment of the state of the neurophysiological, pathophysiological and psychological components of pain is carried out with subsequent impact on all levels of the organization of this system: eliminating the source of pain and restoring damaged tissues; impact on peripheral components of pain - somatic (elimination of inflammation, swelling, etc.) and neurochemical stimulators of pain receptors; inhibition of pain impulses along peripheral nerves; impact on processes occurring in the dorsal horns of the spinal cord, including activation of descending inhibitory effects; impact on the psychological and emotional components of pain.

The cumulative influence on all levels of the organization of the pain system in the treatment of pain as a symptom, regardless of its origin, is almost impossible due to the risk of polypharmacy. In the process of searching for the optimal drug in the 1970s, flupirtine maleate (catadolon) was synthesized, approved for use in 1986. Since then, the drug began to be widely used in clinical practice, and new information was obtained about its therapeutic effect and special properties constantly expanding the scope of its application.

Flupirtine is a centrally acting non-opioid analgesic that selectively acts at the level of interneurons of the dorsal horn of the spinal cord. The first systematic review to evaluate the effectiveness and safety of flupirtine for pain of various etiologies was carried out in 1987 and included multicenter clinical studies that involved 1174 patients who took flupirtine or pentazocine (a synthetic narcotic analgesic) for 3-8 weeks, depending on the indications. . It was noted that flupirtine had greater efficacy and better tolerability compared to pentazocine. It was this study that confirmed the further feasibility of assessing the analgesic effect of flupirtine [cit. according to 9].

The initial stage of the formation of pain syndrome in the form of tissue damage generates the synthesis of arachidonic acid metabolites from adjacent membranes, the cleavage of bradykinin precursors and the release of peptides such as substance P and calcitonin gene-related peptide C-fibers. Inflammation also increases the content of 5-HT, potassium and hydrogen ions, which activate and sensitize peripheral endings and cause vasodilation and plasma permeation, resulting in swelling, pain and increased sensitivity. The concerted effect of these mediators, released in damaged tissues, underlies the signs of inflammation, especially hyperalgesia and pain, swelling and local increase in temperature. The effect of these mediators at the site of tissue injury creates primary peripheral hyperalgesia; the pain is aggravated by their influence on the endings of nociceptive peripheral sensory fibers. The additive effect of other mediators—cytokines, nerve growth factor, catecholamines, and prostaglandins—implies complexity in the peripheral transmission leading to hyperalgesia. The existence of peripheral hyperalgesia is the basis that induces central sensitization in spinal cord neurons [13].

Pathophysiological mechanisms of chronic pain syndrome include peripheral and central sensitization, secondary hyperalgesia, behind which there is a cascade of neurophysiological and neurochemical transformations that ensure the maintenance of this condition. It is generally accepted that primary hyperalgesia is a consequence of sensitization of peripheral multimodal nociceptors at the site of injury, while secondary hyperalgesia is a consequence of plastic changes in the central nervous system [26]. The neuronal sensory system of the dorsal horn of the spinal cord is the largest field of representation of neurotransmitters and their receptors in the spinal cord identified in the central nervous system. Transmitters are released in response to the activity of afferent fibers of spinal neurons or the endings of descending fibers from the brain and become concentrated in the substantia gelatinous, one of the densest fields of the central nervous system, where convergence of perception and modulation of nociceptive information occurs. The activating amino acids glutamate and aspartate, along with some peptides, are involved in nociceptive transmission in the dorsal horn of the spinal cord [13].

Activation of NMDA receptors by glutamate or aspartate causes the opening of NMDA channels, which are permeable not only to sodium and potassium ions, but also to calcium. At a hyperpolarized residual potential, magnesium prevents ions from entering through the NMDA channel, but depolarization of the membrane removes this magnesium block. Thus, NMDA receptors become not only ligand gates, but also potential gates, promoting central sensitization (sustained neuronal depolarization) and chronic pain transmission [27]. An increase in the excitability of nociceptive neurons in the structures of the central nervous system inevitably causes reflex activation of motor neurons in the corresponding segments of the spinal cord and muscle contraction. Prolonged muscle tension through the mechanisms of neurogenic inflammation in the muscle itself contributes to the appearance of loci of painful muscle compactions, which enhances the myogenic afferent flow of nociceptive impulses into the structures of the central nervous system. As a consequence of this, a larger number of central nociceptive neurons are sensitized. This vicious circle plays an important role in the prolongation of pain and the development of the myogenic component of the pain syndrome [5].

Studies have shown that flupirtine in therapeutic doses selectively opens potassium ion channels of neurons, which help the neuron return from a state of depolarization to a state of hyperpolarization, as a result of which the flow of Ca2+ ions into the cell stops and Mg2+ again blocks the NMDA receptor. In this case, the activation of NMDA receptors is indirectly suppressed; The membrane potential stabilizes and the excitability of neurons decreases. There is no transmission of impulses to the central nervous system and no involvement of motor neurons. All this ensures the effect of flupirtine on the afferent processes of the nociceptive neuron, which causes the corresponding clinical manifestations: suppression of nociceptive excitation causes an analgesic effect; blocking the pain impulse at the level of the interneuron; prevents its spread to the motor neuron, which explains the muscle relaxant effect in the area of ​​pain; prevents the transition of acute pain to chronic; The neuroprotective effect of flupirtine is due to the protection of nerve cells from increasing calcium intoxication.

Further studies of flupirtine confirmed indirect functional antagonism with NMDA receptors. It was also shown that flupirtine does not have a direct effect on these receptors [20, 21]. In addition, it has been established that changes in pain perception also occur through the descending noradrenergic system [22, 23]. It has also been shown that flupirtine does not affect potassium channels in the heart muscle, so its use does not have cardiac side effects. It is important that flupirtine has no affinity for NMDA receptors, which results in the absence of psychotropic side effects. It also does not affect opioid mechanisms and does not bind to benzodiazepine receptors, therefore it does not cause dependence or addiction, and does not cause sedation. Of particular importance is the fact that flupirtine has no effect on COX-1 and COX-2, this explains the absence of gastrointestinal and vascular side effects, i.e. Unlike NSAIDs, flupirtine is safe for the gastrointestinal tract and does not affect blood rheology.

The drug has a combination of analgesic and muscle relaxant properties, which is especially important in the treatment of pain of the musculoskeletal system with reflex involvement of the muscular system, up to myofascial pain syndrome [28]. In animal experiments, it was found that the severity of the effects of flupirtine can be placed between the effects of paracetamol, codeine, pethidine and tramadol, on the one hand, and morphine, methadone and detromoramide, on the other [14, 15, 24].

The largest study to evaluate the analgesic effect and tolerability of flupirtine in the treatment of acute and chronic pain associated with muscle tension is an open multicenter study performed by G. Mueller-Schwefe [18]. The study involved 7,806 patients (43% men and 57% women) suffering from various types of back pain, neck pain, tension headaches and myofascial pain syndrome. Treatment was carried out for 4 weeks, 200-300 mg of flupirtine per day. Efficacy and tolerability were assessed by both doctors and patients on a 4-point scale. The results of the study showed that after 4 weeks of treatment, the severity of pain and muscle-tonic syndromes decreased in patients, and their quality of life and emotional status improved. The majority of doctors and patients (more than 90%) rated the tolerability of therapy as very good or good. Multilateral experimental studies have supplemented this information with data on the neuroprotective effect of flupirtine [12, 16, 17, 19, 20].

In order to evaluate the analgesic and muscle relaxant effect of flupirtine in comparison with placebo and chlormesanone (tranquilizer-anxiolytic), R. Worz et al. [28] performed a placebo-controlled study in 184 patients suffering from chronic low back pain. The results of the study showed that 60.9% of patients responded positively to therapy with flupirtine, 47.8% of patients responded positively to therapy with chlormesanone; with placebo therapy, the effect was obtained in 43.8%. According to the physician-researchers, the assessment of “very good/good” in the group of patients taking flupirtine corresponded to the condition of 47.8% of patients, and “satisfactory” - 37.0%. When taking chlormesanone, 45.6% of patients rated the treatment as “very good/good,” while 17.4% of patients received a “satisfactory” rating. An analysis of the safety of treatment revealed the presence of undesirable effects in 14.8% of patients taking flupirtine and 19.3% of those taking chlormesanone; in the placebo group, 7.3% of patients noted undesirable effects. The researchers found that flupirtine has an adequate efficacy and safety profile in patients suffering from chronic low back pain.

The advisability of using flupirtine for pain in the lower back is confirmed by the recommendations of a group of experts led by M. van Tulder, who in 2004 developed guidelines for the relief of acute pain in the lower back [25]. Flupirtine is recommended as a possible alternative therapy, including in combination with non-steroidal anti-inflammatory drugs, to reduce pain and muscle tone.

In our country, a sufficient number of studies have also been carried out to date confirming the effectiveness of the use of flupirtine in acute and chronic pain syndromes, not only vertebrogenic, but also in chronic tension-type headaches, as well as during the period of refusal of analgesic drugs for drug-induced headaches ( abuse headaches) [1-4, 7-11].

Thus, flupirtine (trade name - catadolone) has both analgesic and muscle relaxant effects in acute and chronic pain syndromes and, taking into account the peculiarities of its pharmacological characteristics, can be combined with NSAIDs and antidepressants. For effective treatment of pain syndrome, flupirtine must be prescribed from the first days of treatment, more often in combination therapy. The duration of treatment is usually individual, but given the mechanism of action of the drug, it should be at least 7-14 days, and, if necessary, longer (up to several months).

Instructions for use

The dose and order of administration should be determined by the attending physician; it directly depends on the type of disease and the severity of the pain syndrome. The tablets should be taken orally with a moderate amount of water (half a glass is enough). The rules for taking the drug are as follows:

• people 18-65 years old are given 100 mg up to four times a day, the intervals between treatments should be approximately equal;
• adults with intense pain are prescribed 200 mg (instead of capsules, you can take half a Katadolon Forte tablet), but not more than 3 times a day;
• you cannot exceed the highest dosage per day - 600 mg, if there is renal failure, this figure is 300 mg, for liver failure - 200 mg;

• people over 65 and elderly patients are prescribed no more than 2 capsules/day - morning, evening, if well tolerated and if necessary, the dosage can be increased to 3 capsules/day.

The course of therapy can be long, but only in combination with dynamic medical supervision and regular blood tests for liver fractions.

Application of a new analgesic Katadolon (flupirtine) in clinical practice

Kamchatnov P.R.

The presence of pain is one of the main reasons forcing a patient to see a doctor. The vast majority of patients who seek outpatient care from a doctor complain of pain of various locations; there is also a large number of patients with pain syndromes in a hospital setting. The majority of patients suffer from pain caused by spinal pathology and combined muscular-tonic disorders (osteochondrosis, deforming spondylosis, osteoporosis, etc.), however, there are a large number of other causes of pain, caused by lesions of the peripheral, and less often, central nervous system. An important problem is headaches, in particular tension headaches, which are also extremely common in neurological patients. The exceptionally wide prevalence of pain syndromes dictates the need to search and develop new ways to effectively relieve pain and, if possible, eliminate the causes of pain. Timely and adequate treatment of acute pain syndrome is fundamentally important in order to prevent chronicity of the pathological condition.

Among the drugs used in clinical practice, the most widely used are analgesics (paracetamol), non-steroidal anti-inflammatory drugs (diclofenac), muscle relaxants (tizanidine), in some cases anticonvulsants (eg carbamazepine), antidepressants are prescribed. The choice of drugs, their combinations, methods of administration and dosage are largely determined by the patient’s condition, the characteristics of the clinical picture and their tolerability. Unfortunately, the prescription of painkillers and anti-inflammatory drugs significantly increases the likelihood of complications, primarily from the gastrointestinal tract, especially in the presence of associated risk factors. As a result, the interest in finding new drugs with high clinical efficacy with a relatively low risk of side effects is understandable. In this regard, the drug catadolon (flupirtine), which has a wide range of valuable pharmacological properties that allow its use in internist practice, seems quite promising.

Catadolon is the prototype of a new class of drugs, selective activators of neuronal potassium channels (“Selective Neuronal Potassium Channel Opener” - SNEPCO). In terms of its pharmacological effects, the drug is a non-opioid analgesic of central action, which does not cause dependence or addiction; in addition, it has a muscle relaxant and neuroprotective effect. Chemically, catadolone belongs to the group of triaminopyridine derivatives.

As a result of a large number of experimental studies, it was established that the basis of the action of catadolon is the activation of voltage-independent potassium channels, which leads to stabilization of the membrane potential of the neuron. It has been established that the effect on the current of potassium ions is mediated by the effect of the drug on the regulatory G-protein system, and the effect develops at therapeutic concentrations of the drug achievable in clinical settings (11). Due to the developing suppression of neuronal excitation in response to nanociceptive stimuli, inhibition of nociceptive sensitization, an analgesic effect is realized, which prevents the transition of pain to a chronic form, and in the case of an existing chronic pain syndrome, leads to a decrease in its intensity.

Of exceptional interest is the ability of catadolone to influence the activity of aminoacidergic nerve transmission. Considerable factual material accumulated during experimental studies allows us to consider suppression of the activity of NMDA receptors, along with the effect on the transmembrane transport of potassium ions, as the leading mechanism of action of the drug (25).

It has been established that both intraperitoneal and intrathecal administration of catadolone causes inhibition of polysynaptic reflexes, similar to that observed with other drugs that have an antagonistic effect on NMDA receptors (26). Due to the suppression of NMDA receptors, when catadolone is administered, a decrease in the intracellular concentration of calcium ions develops (18). The authors suggested that the antagonism of catadolone in relation to NMDA receptors is not direct, but indirect. Confirmation that the drug in clinical settings does not interact directly with NMDA receptors is the fact that their blockade occurs only at very high concentrations (200 or more μM), which is unattainable in clinical settings (11).

Indirect confirmation of the antagonism of catadolone in relation to NMDA receptors is the neuroprotective effect provided by the drug in conditions of ischemia of brain tissue and its toxic damage (19, 23). It should also be noted that there is data on the use of the neuroprotective effect of catadolon in various models of experimental parkinsonism (26), as well as some other neurodegenerative processes (28).

The results of experimental studies available to date convincingly indicate that the analgesic effect of catadolone is not associated with interaction with the opiate and benzodiazepine prescription system, as well as the metabolism of arachidonic acid and the suppression of prostaglandin synthesis (3, 4, 17). The absence of suppression of prostaglandin synthesis seems to be an extremely important property of catadolone, because as a result, it does not affect the condition of the gastrointestinal mucosa, and its use is not associated with such complications from the use of non-steroidal anti-inflammatory drugs as Lyell's syndrome, pancytopenia, agranulocytosis (8, 29).

There is evidence that catadolone has an analgesic effect both due to indirect antagonism of NMDA receptors and through the modulation of pain mechanisms associated with effects on GABAergic systems. It is also possible that catadolon modulates the perception of pain through the descending noradrenergic system (30). Experimental data indicate that catadolon affects various parts of the pain perception system, in particular, at the spinal and supraspinal (thalamic) levels (1, 2). The antispastic effect of catadolone is due to the effect on the striated muscles, mediated by blocking the transmission of excitation to motoneurons and intermediate neurons. To a large extent, the muscle relaxant effect may be mediated by stimulation of GABAA receptors (32).

Of great interest are the neuroprotective properties of the drug, due to the existence of antagonism towards NMDA receptors and blocking the “glutamate-calcium cascade”, inhibition of apoptosis processes, which was convincingly demonstrated in an experiment on a culture of nervous tissue (20). Catadolone is also believed to have antioxidant effects (6).

After oral administration, catadolon is quickly and almost completely (up to 90%) absorbed from the gastrointestinal tract. The half-life of blood plasma is about 7 hours (10 hours for the main substance and the active metabolite), which is sufficient to provide a lasting analgesic effect. The concentration of the active substance in the blood plasma is proportional to the dose. In patients over 65 years of age, the half-life increases to 14 hours with a single dose and 18.6 hours when taking catadolone for 12 days; the maximum concentration of the drug in the blood plasma is correspondingly 2-2.5 times higher than in young people. About 75% of the administered dose is metabolized in the liver. The drug is excreted from the body mainly (69%) by the kidneys (25% is excreted unchanged), a small part is excreted by the bile ducts.

The effectiveness of catadolone was established in a number of multicenter studies conducted in a number of Western European countries (Germany, Great Britain, Italy), in which the effectiveness of the drug was compared with placebo or known painkillers that meet the principles of evidence-based medicine (randomized multicenter studies) (5, 9) . The effectiveness of catadolone has been established in patients with various causes of pain - those who have undergone surgery (21), those suffering from cancer (24), migraines (15), and diseases of the musculoskeletal system (13). A comparative study of the analgesic effect of catadolone and tramadol in a group of patients with cancer of various locations demonstrated that the use of catadolone 400-600 mg per day had a more pronounced effect than taking tramadol (50 mg per day), as evidenced by a more pronounced decrease in pain intensity in accordance with the visual analogue scale and a reduction in the need for additional use of analgesics (the differences were significant) (12). Side effects in the form of general weakness, sensations of heat occurred in 6% of patients receiving catadolone and in 19% of patients receiving tramadol.

Since the mid-1980s and studies of the drug's effectiveness are being conducted in the United States. Thus, the effectiveness of using the drug for relieving pain syndromes in patients who underwent surgery, episiotomy, and tooth extraction was studied. All studies were conducted using a double-blind method, were multicenter and included two control groups - placebo and a drug with analgesic properties (codeine, paracetamol, their combination, oxycodone, pentazocine). The results obtained in all series of observations allowed us to establish the effectiveness of catadolon, which was significantly higher than that of placebo (14). In addition, the authors noted a rapid onset of analgesic effect, already after taking the first dose. Studies have shown that the analgesic effect resulting from the use of 200 mg of catadolone per day is equivalent to that of 60 mg of codeine. It should also be noted that in a study that included patients with rheumatic soft tissue lesions, the effectiveness of catadolone at a daily dose of 300-400 mg over an 8-week course of therapy was equivalent to 150 mg of pentazocine (22).

The effectiveness of catadolone has also been studied in patients with dorsopathies and various myofascial syndromes. The results obtained indicate that the drug has a pronounced analgesic effect, as well as its good tolerability. It seems important that the positive effect of using catadolone was observed in patients with both acute and chronic dorsopathies, and in patients with chronic and subacute pain syndrome there was an increase in the analgesic effect during treatment (32). In addition to the analgesic effect of the drug, the patients’ condition was facilitated by a decrease in the initially increased muscle tone, especially in muscular-tonic and myofascial syndromes (10). An important feature of the use of catadolone was the absence of the development of muscle weakness during treatment in the vast majority of patients. In patients with vertebrogenic dorsopathies, relief of acute pain syndrome is accompanied by normalization of the emotional state and restoration of night sleep, which leads to an increase in the quality of life of patients (16).

A multicenter, open-label study that included 869 patients examined the effectiveness of catadolon in patients with osteoporosis in outpatient settings (22). Patients received catadolone 100 mg 3 times a day, the course of treatment ranged from 2 to 4 weeks. According to the visual analog pain scale, the initial level of pain in the lumbar spine was 7.1 points, in the neck – 5.8 points, and in the shoulder girdle – 5.6 points. The decrease in the severity of pain by the end of the course of therapy was, respectively, 44%, 40% and 43% (all differences were significant compared to the initial level). Just like most other studies, the authors noted that the drug was well tolerated - side effects occurred in 2.4% of those observed, only 12 (1.2%) required discontinuation of treatment due to the appearance of general weakness, drowsiness, dizziness, and discomfort in the epigastric region .

There are reports of the use of catadolone in patients with tension headaches. Thus, in a multicenter, double-blind, placebo clinical study that included 143 patients aged 18 to 65 years (average 44.1 + 11.8 years), it turned out that the use of catadolon for two weeks daily 100 mg three times a day was found to significantly reduce the intensity and daily duration of headaches. At the same time, a tendency towards normalization of the emotional state and restoration of night sleep was recorded. Undesirable side effects in the form of general weakness, drowsiness, which did not require a change in the drug regimen, were observed in 17.5% of patients receiving catadolone and in 16.6% receiving placebo (31).

Katadolon is well tolerated. Side effects such as a feeling of general weakness, drowsiness or difficulty falling asleep, transient nausea are observed relatively rarely and occur with long-term (many months) regular use of the drug (7). Thus, observation of 7,806 patients with pain syndromes (dorsopathies, cervicalgia, tension headaches) receiving catadolon revealed that side effects were recorded in 0.9% of cases (general weakness and dizziness) (16). When catadolone was prescribed for more than four weeks, the maximum number of unwanted side effects was recorded during the first and second months of treatment and subsequently decreased during treatment (by the 12th month) (8).

As a result of the analysis of the results of long-term (lasting up to 12 months) studies, no addiction to the drug or the occurrence of physical dependence on it was registered (7, 8). There were also no significant clinical manifestations of withdrawal syndrome, even in the case of long-term use of catadolone. Observation of patients who took catadolon for a long time for two weeks after stopping treatment did not reveal changes in emotional status or autonomic disorders that could be regarded as manifestations of withdrawal syndrome.

Catadolon in the form of capsules containing 100 mg of flupirtine maleate is registered in the Russian Federation. In addition, the drug is produced in Germany in the form of rectal suppositories for adults containing 150 mg of flupirtine maleate and for children containing 164.5 mg of flupirtine-D-gluconate, which is equivalent to 100 mg of flupirtine maleate (not registered in Russia). In Germany, the drug has been approved for use since 1986. Rich clinical experience has been accumulated in this country. Catadolon is included in the recommendations for drug therapy for back pain developed by the German Association for the Study of Pain and the German Association of Rheumatology (Table 1) [36].

Table 1. Drugs of choice for the treatment of back pain [36]

The drug is used at a dose of 100 mg (1 capsule), without chewing and with a small amount of liquid (100 ml) 3-4 times a day with an equal interval between doses. For severe pain, you can take 2 capsules 3 times a day. The maximum daily dose should not exceed 600 mg (which corresponds to 6 capsules). The use of catadolone, if necessary, can be combined with the prescription of non-steroidal anti-inflammatory drugs, muscle relaxants, and antidepressants. Contraindications for use are individual hypersensitivity, severe liver failure with symptoms of encephalopathy, cholestasis, myasthenia gravis, alcoholism with damage to internal organs, pregnancy, age under 18 years.

The data presented indicate the high effectiveness of the drug catadolon, comparable to that of a number of drugs used in clinical practice for the relief of pain syndromes. Katadolon can be used to treat patients primarily with chronic and subacute back pain, cephalgia, in particular tension headaches, as a symptomatic therapy for pain caused by malignant neoplasms. An extremely important feature of the drug is its good tolerability and the absence of damaging effects on the mucous membrane of the stomach and duodenum. It seems obvious that the combination of these properties of catadolone will ensure the possibility of its use in clinical practice.

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Side effects and contraindications

The drug is prohibited during lactation, pregnancy, and children under 18 years of age.

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It is given with caution to people over 70 years of age and only for strict indications. For any dysfunction of internal organs, the drug is also used carefully, under the supervision of a specialist. Contraindications to therapy are also:

• disorders of bile secretion;
• cirrhosis of the liver;
• fatty hepatosis;

• chronic alcohol abuse;
• hypersensitivity to the main and additional components;
• asthenic bulbar palsy.

As with other analgesics, the most common side effects of Katadolon affect the digestive system. These are nausea, vomiting, stomach pain, constipation, diarrhea and other digestive disorders. A number of people lose their appetite and have dry mouth. During administration, AST and ALT of the liver may increase, returning to normal after the end of therapy. In especially severe cases of “side effects,” drug-induced hepatitis with jaundice develops. In 0.1% of cases, allergies and skin itching occur.

Why was Katadolon discontinued?

The European Pharmacological Regulatory Authority (PRAC) has recommended stopping the marketing and use of the non-opioid analgesic catadolone. The drug is prescribed as a pain reliever in extreme cases, when taking other pharmacological products is impossible for some reason.

Previously, catadolon was prescribed with great caution. The drug was always prescribed with a number of conditions:

• it is unacceptable to take more than 14 days;
• if necessary, replace the non-opioid analgesic with other painkillers;
• carefully monitor the patient's well-being.

Ban on analgesic

A significant reason why catadolon was banned from use in modern therapeutic regimens is that the risks of taking the drug significantly outweigh the benefits of taking it.

The main threat is liver damage. Hepatocytes suffer not only from the oral form of the drug, but also from suppositories.

Another reason why catadolon was discontinued is that it is often used as a specific “relaxation” substance. The addiction set in quickly, and my health deteriorated.

Analogues and other information

There are cheaper drugs that can serve as a substitute for this remedy.

A number of analogues are produced with the same active substance, others belong to other medicinal groups.

The medicine can increase the strength of the influence of alcohol, sleeping pills, and sedatives, which must be taken into account when prescribing and conducting therapy. If you are prone to liver damage, it may be recommended to take enzyme agents in addition to taking Katadolon. Katadolon tablets interact poorly with Paracetamol drugs, with muscle relaxants, and enhance the effect of blood thinners.