Betalgon
Betalgon Uses, Dosage, Side Effects, Food Interaction and all others data.
Nicoboxil has been investigated for the treatment of Acute Low Back Pain, where it is typically considered an effective and safe therapeutic option. Nevertheless, it is predominantly found paired with nonivamide as a combination topical analgesic product where its proposed mechanism of action as a rubefacient is complementary and ultimately synergistic with nonivamide's capsaicin activity . Such combination topical analgesics are only available for purchase and use (for humans) in some parts of Europe and Asia, like Germany and Australia .
Despite topical nicoboxil/nonivamide topical analgesic medication being used since the 1950s, recent studies demonstrate continued interest in the medication(s) given its demonstrated efficacy, safety, and capability to be used as an alternative musculoskeletal pain therapy option with less systemic side effects when compared to the oral non-steroidal anti-inflammatory drugs and opioids that may be more typically prescribed .
Topical applications consisting of the individual active ingredients of nicoboxil and nonivamide at doses considered to be therapeutic are generally not considered readily available commercially . Subsequently, the pharmacodynamics of nicoboxil are considered useful in commercially available combination products largely because they combine with those of nonivamide to offer a synergistic effect from the unique complementary actions of these two agents .
Nonivamide is found in herbs and spices. It is an alkaloid from the Capsicum species. The structures of Capsaicin and nonivamide differ only slightly with respect to the fatty acid moiety of the side chain (8-methyl nonenoic acid versus nonanoic acid) .
Nonivamide is a flavoring ingredient. Nonivamide is an organic compound and a capsaicinoid. It is an amide of pelargonic acid and vanillylamine. It is naturally found in chili peppers but manufactured to produce a synthetic form for various pharmacologic preparations .
This drug has been studied in combination with Nicarboxil in the treatment of lower back pain .
| Trade Name | Betalgon |
| Generic | Nicoboxil + Nonivamide |
| Type | |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Russia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Nicoboxil is a medication used to treat acute back pain.
The primary therapeutic use for which nicoboxil is currently indicated for is as an active ingredient in combination with the capsaicinoid nonivamide compound as a topical analgesic for the temporary relief of the pain of rheumatism, arthritis, lumbago, muscular aches, sprains and strains, sporting injuries, and other conditions where local warmth is beneficial .
Nevertheless, most of the available studies regarding the use of nicoboxil and nonivamide topical analgesics focus specifically on their efficacy and safety in treating acute non-specific low back pain, typically finding the combination analgesic to be an effective, safe, and well-tolerated medication for such an indication .
Nonivamide is used as a topical analgesic and is also used as a flavoring ingredient , , .
Betalgon is also used to associated treatment for these conditions: Back Pain Lower Back, Back Pain, Acute, Contusions, Joint Pain, Rheumatism, Soreness, Muscle, Sprains, Stiff Shoulder, Poor blood circulation, Topical Analgesia
How Betalgon works
In particular, nicoboxil is considered a rubefacient . However, the specific mechanism of action by which rubefacients like nicoboxil elicit pharmacologic effects has not yet been formally elucidated . Nevertheless, it is generally proposed that rubefacients cause irritation of the skin when applied topically, and are believed to alleviate pain in muscles, joints, tendons, and other musculoskeletal pains in the extremities by counter-irritation . This specific term, 'counter-irritant', derives from the fact that rubefacients can cause a reddening of the skin by causing the blood vessels of the skin to dilate, which gives a soothing feeling of warmth . In essence, the term largely refers to the notion that irritation of the sensory nerve endings alters or offsets pain in the underlying muscle or joints that are innervated by the same nerves .
In fact, the vasodilation effect of rubefacients like nicoboxil has been considered the result of nerve conduction mechanisms as early as the late 1950s when certain studies demonstrated that the concomitant application of xylocaine could counteract or prevent the vasolidator response to rubefacients in 50% of such related experiments .
Nonivamide is a naturally occurring analog of Capsaicin, isolated from peppers, described to produce effects similar to Capsaicin. It is an agonist of the VR1 (vanilloid/TRPV1 receptor) . It serves as a transient agonist of these receptors, which are potentiated by pro-inflammatory drugs, a phenomenon that leads to thermal hyperalgesia, or increased heat sensation .
Nonivamide has been shown to stimulate afferent neurons with about half the potency of Capsaicin. Agonism of the VR1 (TRPV1) (vanilloid) receptor by Nonivamide was demonstrated to induce the release of Ca2+ from the endoplasmic reticulum (ER) of human lung cells, producing ER stress and cell death .
Nonivamide, like other capsaicinoids, acts on the vanilloid receptors located in the peripheral afferent nerve fibers, providing short-acting irritant and algesic properties. Applied dermally, these substances act by stimulating sensitive chemoreceptors of the skin and by reflex, hyperemia and a local elevation in temperature. After repetitive administration, capsaicinoids have been reported to lead to desensitization to nociceptive stimuli possibly by long-acting depletion of peptide neurotransmitters (substance P) from peripheral sensory neurons. Capsaicinoids can modulate muscle tone (in bladder, bronchus etc.). Intravenous injection of nonivamide to rats (10 μg/kg) has been found to lead to bradycardia. The cardiovascular effects are partly explained by substance P release. Nonivamide given to rats subcutaneously (1 mg/kg) was found to cause body temperature decrease, vasodilatation, and increased salivation. Capsaicinoids have shown to illicit bronchospastic effects in guinea pigs. Capsaicin and its analogs were reported to increase barbiturate sleeping time in rats by interacting with hepatic metabolizing enzymes .
Toxicity
Nicoboxil is of low acute toxicity . No adverse side effects were reported in humans after therapeutic use of the combination of nicoboxil/nonivamide . In a study using dermal application of nicoboxil/nonivamide in over 1000 patients, no allergic reactions were observed .
Nonivamide appears to be of low acute toxicity, according to the EMA summary report . The oral LD50 in rats is reported with 5110 mg/kg and the dermal LD50 in rabbits is greater than 10 000 mg/kg. Administered intraperitoneally, the LD50 in rats was measured to be about 90 mg/kg. In combination with nicoboxil, the acute dermal toxicity of nonivamide was increased. Signs of toxicity (depression, labored respiration, diarrhea) were observed at doses as low as 32 mg/kg body weight of nonivamide combined 200 mg nicoboxil/kg body weight .
Allergic reactions in humans following administration of capsaicin or capsicum extracts are reported to be rare .
No information on carcinogenic properties of nonivamide was available. Tumorigenic properties have been reported in literature for Capsaicin or chili .
Volume of Distribution
Despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing . Readily accessible data regarding the volume of distribution of nicoboxil is subsequently not available.
Elimination Route
Specific investigations on absorption of dermally applied nicoboxil in laboratory animals or target species were not available . Published data for nicotinate esters related to nicoboxil indicated however, that members of this class of compounds are in principle able to penetrate skin [12].
Regardless, there is interest in the studies that demonstrate nicoboxil and nonivamide combination topical applications as effective and safe analgesic products precisely because such topical formulations are expected to have much lower systemic absorption - and thus less exposure to systemic side effects (ie. like gastrointestinal upset, drowsiness, etc.) - than the oral non-steroidal anti-inflammatory drugs, opioids, muscle relaxants, and steroids that may be more commonly prescribed over a rubefacient like nicoboxil .
Nevertheless, despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing .
Half Life
The half-life of ester hydrolysis was found to be very short in the presence of human serum albumin - less than 15 minutes, 50uM .
About 7 minutes .
Clearance
The elimination of nicoboxil is considered to be rapid .
Despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing . Readily accessible data regarding the clearance of nicoboxil is subsequently not available.
Elimination Route
Following ester cleavage, the nicotinic acid metabolite is expected to enter the endogenous metabolic pool as a part of the vitamin B complex . The 2-butoxyethanol metabolite is believed to be mainly excreted primarily in the urine and to a certain extent, in exhaled air . In humans, the urinary elimination of 2-butoxyethanol's metabolite, 2-butoxyacetic acid was also reported .
Innovators Monograph
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