2-Butoxyethyl 3-pyridinecarboxylate

223.26800

223.27

237-684-7

GSD5B9US0W

DTXSID4057635|DTXSID4057895

2933399090

48.42000

2.05510

1.066g/cm3

287.4ºC

127.6ºC

1.494

0.00248mmHg at 25°C

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 5 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

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.

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 protein binding of nicoboxil is subsequently not available.

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.

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. Subsequently, nonivamide is a synthetic capsaicin analog with analgesic properties which are assumed to result from the depletion of Substance P in the peripheral nociceptive C-fibres and A-delta nerve fibers upon repetitive topical application. Resultant stimulation of afferent nerve endings in the skin evidently causes a dilatory effect on the surrounding blood vessels accompanied by an intense, long-lasting sensation of warmth associated with the nonivamide use. Given the proposed effect of nonivamide, it is believed that nicoboxil is a vitamin of the B complex that possesses vasodilating properties facilitated by prostaglandin. The observed hyperaemic increased blood flow effect of nicoboxil occurs earlier and is described as being more intense than the nonivamide hyperaemic effect. Nicoboxil and nonivamide are consequently generally indicated as a combination product because the pharmacodynamics of nicoboxil are considered useful as a complement to those of nonivamide, and vice versa. In essence, both compounds induce vasodilation by different effects and therefore have complementary abilities inducing increased blood flow, thus hastening the hyperaemic skin reaction.

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.|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.|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.|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.

Any systemically absorbed nicoboxil is expected to be hydrolyzed to nicotinic acid and 2-butoxyethanol in blood plasma. In vitro it is reported that such hydrolysis reactions are catalyzed by esterase-like activity of serum albumin and by plasma esterases. The nicotinic acid metabolite is also capable of vascular dilatation. In humans, the urinary elimination of 2-butoxyethanol's metabolite, 2-butoxyacetic acid was also reported. The metabolism of nicoboxil is considered to be rapid.

The half-life of ester hydrolysis was found to be very short in the presence of human serum albumin - less than 15 minutes, 50uM.

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.

2-butoxyethyl nicotinate

Cosmetics -> Skin conditioning