Methyl Nicotinate Research Articles

Optimisation of a dosing regime for a topical skin protectant (barrier cream)

Context: Topical skin protectants (barrier creams) have the potential to reduce or enhance the severity of dermal lesions following exposure to allergens or irritants. Therefore, it is essential that such products are subject to appropriate clinical evaluation prior to marketing. Consequently, it is important to accurately define a dosing regime in order to assess test products under appropriate conditions.Objective: In this study, we extended the use of a standard rubefacient (methyl nicotinate; MN) assay to establish the optimum thickness and duration of action of a novel barrier cream (RD1433). White petroleum jelly (Vaseline®) was used as a comparator product.Methods: The dermal response to MN was measured on the volar forearm skin of volunteers (n = 12; average age 47.5 years) using an array of biophysical instruments and visual scoring. When applied at a nominal thickness of 0.1 mm, RD1433 retained effectiveness against MN for up to six hours. In contrast, Vaseline® was relatively ineffective. Moreover, RD1433 provoked no measurable signs of irritation and so can be considered acceptable for further clinical evaluation.Conclusion: Future clinical studies using RD1433 should be based on topical application of a 0.1 mm thickness layer every six hours.

McLafferty-type rearrangement of protonated N-[nicotinoyl]phenylethyl amines and consequent elimination of styrene.

McLafferty rearrangements occur in radical cations of molecules containing a carbonyl group and a γ hydrogen atom but are not common in the [M+H](+) ions of carbonyl compounds. We propose to investigate the collision-induced dissociation (CID) of the [M+H](+) ions of nicotinoyl and picolinoyl amides of 1- and 2-phenylethylamines to explore the possibility of McLafferty-type rearrangement. The compounds for study were synthesized by the reaction of methyl nicotinate or methyl picolinate with 1- and 2-phenylethylamines. The CID mass spectra of electrospray ionization (ESI)-generated protonated molecules were obtained using a QSTAR XL quadrupole time-of-flight (QTOF) mass spectrometer, and density functional theory (DFT) calculations using the B3LYP method were employed to elucidate the fragmentation mechanisms. The total electronic and thermal energies of intermediate transition states (TSs) and product ions are reported relative to those of the [M+H](+) ions. CID of the [M+H](+) ions of N-[nicotinoyl]-2-phenylethylamine (1) yielded product ions of m/z 105 (1-phenylethyl cation) and 123 ([M+H-styrene](+) cation). The competitive formation of the ions of m/z 123 and 105 is proposed to involve a McLafferty-type rearrangement. Similarly, the [M+H](+) ions of the isomeric compound 2 and the N-[picolinoyl] phenylethyl amines (3 and 4) dissociate to yield ions of m/z 123 and 105. A molecule of styrene was eliminated from the ESI-generated [M+H](+) ions of N-[nicotinoyl]phenylethylamines and the isomeric N-[picolinoyl]phenylethylamines, through a mechanism involving a McLafferty-type 1,5-H shift. The transition state energy for the 1,5-H shift is less for the amides of 1-phenylethylamine than for the amides of 2-phenylethylamine. The process occurs as a charge remote process and the presence of the pyridine ring is essential for the process.

Electrodeposition of Bright Al Coatings from 1-Butyl-3-Methylimidazolium Chloroaluminate Ionic Liquids with Specific Additives

The electrodeposition of aluminum (Al) on copper (Cu) substrate was investigated in [Bmim]Cl/AlCl3 (33.3/66.7 mol%) ionic liquid using three pyridine derivatives, nicotinic acid, methyl nicotinate, and 3-methyl pyridine as additives at 303 K, respectively. It was found that bright Al coatings could be electrodeposited with nicotinic acid and methyl nicotinate as additives. SEM and XRD characterizations revealed that the bright coatings were very smooth, composed of nanocrystalline and with a strong (200) preferential orientation. By contrast, a matte and lusterless Al coating was obtained from the ionic liquid with 3-methyl pyridine. Furthermore, the effect of the three additives was investigated by means of cyclic voltammetry, chronopotentiometry and Raman spectroscopy. It was demonstrated that nicotinic acid and methyl nicotinate could absorb on electrode surface more easily and thus served as very effective brighteners producing highly uniform and smooth Al coatings. However, 3-methyl pyridine had no such effect.

Exploring human in vivo microcirculation with methyl nicotinate in different perfusion conditions

Exploring human in vivo microcirculation with methyl nicotinate in different perfusion conditions

The Relationship between Impaired Methylnicotinate Response and Oxidative Stress in Schizophrenia

MNA response applied methylnicotinate (MNA) results in an arachidonic acid and cyclooxygenase-dependent vasodilatatory response which is diminished in patients with schizophrenia. This observation has been suggested to form the basis of a diagnostic test for the illness although the potential utility of such a procedure is diminished since the underlying mechanism is unclear. In this study we sought to discover if reduced MNA response in schizophrenia is related to increased oxidative stress i.e. whether or not the two measures are negatively correlated with each other. MNA response was assessed visually in 17 patients with schizophrenia and 16 healthy controls and compared to the extent of oxidative stress in each participant assessed by quantifying the lipid peroxidation product ethane in breath. Serum vitamin E, a lipid soluble antioxidant, concentrations was also assessed. While MNA response was correlated with breath ethane concentrations, the expected relationship between the two measures was not observed. Instead a positive relationship between them suggests that some patients with schizophrenia have impaired fatty acid utilization leading to both diminished lipid peroxidation and cyclo-oygenation. This was not related to vitamin E concentrations, however, suggesting that lipid soluble anti-oxidant availability did not underlie our findings. Our data shed further light on the mechanism of impaired MNA response in schizophrenia and support the notion that this occurs consequent to a change in lipid metabolism.

Fingerprinting Breath: Electrochemical Monitoring of Markers Indicative of BacteriaMycobacterium tuberculosisInfection

Recently it has been shown that chemical markers in exhaled air/breath can provide a methodology for the detection of tuberculosis infection. These markers consist of methyl phenylacetate, methyl p-anisate, methyl nicotinate and o-phenylanisole (2-methoxybiphenyl). Current approaches utilise gas chromatography-mass spectrometry (GCMS) which are useful for centralised testing of breath samples. The World Health Organization (WHO) require a portable, non-invasive diagnostic tool for the screening of tuberculosis infection. In order to meet this, we demonstrate proof-of-concept for the analytical sensing of the identified chemical markers in aqueous solutions using electrochemical based technology. We demonstrate that screen-printed electrochemical sensors can be used as the basis of a diagnostic tool for the electrochemical breathprinting of chemical markers (methyl nicotinate and 2-methoxybiphenyl) useful for the screening of tuberculosis infection. It is hoped that further development will facilitate the potential for a portable, hand-held, non-invasive breath diagnostic tool to be realised.

Comfrey root extract in combination with methylnicotinate in the treatment of acute upper or lower back pain: Results of a double-blind, placebo-controlled, multicenter, three-arm RCT

Several RCTs have confirmed the efficacy of comfrey root extract (Symphytum officinale L.) (CRE) in painful muscle and joint complaints. The topical pharmacotherapeutic approach has also included hyperaemising drugs to relax the contracted muscle area. Thus, the extract has also been used in combination with methylnicotinate (MN). The objective was to show the superiority of a CRE plus MN cream (Kytta-Balsam® f) to MN and placebo cream in patients with acute upper or low back pain. In this RCT 379 patients were assigned to three groups (combination of 35% CRE plus 1.2% MN, n = 163; MN, n = 164; placebo, n = 52) and applied a 12 cm layer of cream 3 times daily for 5 days. The trial included four visits. The primary efficacy variable was the AUC (area under the curve) of the VAS (Visual Analogue Scale) on active standardised movement values at visits 1 to 4. Patients performed standardised, muscle group specific tests. Secondary measures included back pain at rest, pressure algometry, consumption of analgesic medication, functional impairment measured with Oswestry Disability Index, and global assessment of response. The AUC of the VAS on active standardised movement was markedly smaller in the combination treatment group than in the MN and the placebo group (ANOVA: p < 0.0001). The pairwise comparisons of the mean AUCs of VAS sums showed values 27% lower in favour of the combination compared to MN, and values 50% lower in favour of the combination compared to placebo. MN alone reached a reduction in this variable of 31% compared to placebo. All pairwise comparisons were statistically significant (t-test: p < 0.0001). The results were consistent across the primary and all secondary variables. Patients treated with the combination had significant superior reductions in pain scores and were more satisfied with the treatment effect. The combination demonstrated superiority to the two other treatment arms, while methyl nicotinate displayed a considerable effect as well.

Validating a breath collection and analysis system for the new tuberculosis breath test

Mycobacterium tuberculosis releases four volatile compounds, methyl phenyl-acetate, methyl nicotinate, methyl p-anisate and o-phenylanisole, some of which we have previously been reported to be detected in the breath of tuberculosis patients (Syhre et al 2009 Tuberculosis 89 263–6). These volatiles have the potential to offer a non-invasive and sensitive breath test for the detection of tuberculosis infection. To determine the best sample collection and pre-concentration system a number of variables were examined. The four markers were most stable when breath was collected in a salinized glass sampling bulb compared to either Tedlar® TA, SupelTM Inert Foil or SupelTM Inert Gas bags. Concentration of breath onto thermal desorption cartridges indicated that Tenax® TA was the most universal sorbent for the collection of all four volatiles. Increasing the number of breath exhalations captured and analysed actively increased the detectable level of volatiles. The most important discovery was samples of methyl nicotinate, methyl p-anisate and o-phenylanisole remained stable on Tenax® TA cartridges for over two months at various altitudes.

Diagnostic potential of the pulsed discharged helium ionization detector (PDHID) for pathogenic Mycobacterial volatile biomarkers

Pathogenic Mycobacteria cause diseases in animals and humans with significant economic and societal consequences. Current methods for Mycobacterial detection relies upon time- and labor-intensive techniques such as culturing or DNA analysis. Using gas chromatography and mass spectrometry, four volatile compounds (methyl phenylacetate, methyl p-anisate, methyl nicotinate and o-phenyl anisole) were recently proposed as potential biomarkers for Mycobacteria. We demonstrate for the first time the capabilities of a field-deployable, pulsed discharge helium ionization detector (PDHID) for sensing these volatiles. We determined the analytical performance of the PDHID toward these Mycobacterial volatiles. Detector performance was moderately affected over the temperature range of 150 to 350 °C. The linear dynamic range for all four analytes exceeded three orders of magnitude. The limits of detection (LOD) and quantitation (LOQ) were calculated as 150 and 450 pg respectively, for all compounds, except methyl phenylacetate (LOD and LOQ, 90 and 270 pg, respectively). Control charts revealed that the PDHID detection system was generally stable, and deviations could be traced to common causes and excluded special causes. Grob tests and ionization potential data suggest that the PDHID is capable of detecting Mycobacterial volatiles in a complex milieu such as culture headspace or breath samples from tuberculosis patients. The diagnostic potential of the PDHID is critical to our goal of a handheld, field-deployable ‘sniffer’ system for biological pathogens and chemical warfare agents.

Evaluation of the gastroprotective activity of 3-carbomethoxypyridine from Pyrenacantha staudtii Engl. (Icacinaceae) in rats

3-carbomethoxypyridine (3-CMP, also known as methyl nicotinate) is a compound isolated and characterized from the leaves of a local plant, Pyrenacantha staudtii Engl. (Icacinaceae), and known to possess anti-ulcer effects. The present study was undertaken to evaluate the possible gastroprotective effects of 3-CMP. Various models of ulcer such as pylorus ligation ethanol-, ethanol/HCl- and indomethacin-induced ulcer in rats were employed. Anti-ulcer effect was assessed on the basis of the number of reduction in gastric mucosal lesions, increase in pH, and decrease in volume, free and total acidity of gastric juice. The compound produced a non-dose dependent protection of the gastric mucosa in ethanol-, ethanol/HCl- and indomethacin-induced ulcerations with the highest effect at 25mg/kg. 3-CMP significantly decreased the secretion of gastric aggressive factors; free acidity and total acidity as well as superoxide dismutase and catalase. Results obtained suggest that 3-CMP has anti-ulcer and antioxidant properties which may be attributed to its ability to reduce total acidity and free acidity, or mediated through the production of prostaglandins and free radical scavengers which protect the gastric mucosa.Keywords: 3-Carbomethoxypyridine; Pylorus ligation; Indomethacin; Ethanol; Ranitidine; Catalase

Synthesis and antifungal evaluation of (1,2,3-triazol-4-yl)methyl nicotinate chitosan

With an aim to discover novel chitosan derivatives with significant activities against crop-threatening fungi, (1,2,3-triazol-4-yl)methyl nicotinate chitosan (TAMNCS) was prepared via azide-alkyne click reaction. Its structure was characterized by FT-IR, 1H NMR, elemental analysis, DSC, and SEM. In vitro antifungal properties of TAMNCS against Rhizoctonia solani Kühn (R. solani), Stemphylium solani weber (S. solani), and Alternaria porri (A. porri) were studied at the concentrations ranged from 0.25mg/mL to 1.0mg/mL. Experiments conducted displayed the derivative had obviously enhanced antifungal activity after chemical modification compared with original chitosan. Moreover, it was shown that TAMNCS can 94.2% inhibit growth of A. porri at 1.0mg/mL, while dose at which the fungicide triadimefon had lower inhibitory index (62.2%). The primary antifungal results described here indicate this derivative may be a promising candidate as an antifungal agent.

A new molecular silver precursor for the preparation of thin conductive silver films

The synthesis and characterization of a new molecular silver precursor is reported. The presented complex [Ag(DioxoNic)2]NO3 (DioxoNic=(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl nicotinate) can be obtained by the reaction of silver(I) nitrate and (2,2-Dimethyl-1,3-dioxolan-4-yl)methyl nicotinate in ethanol. The product crystallizes in the monoclinic space group P21/c (No. 14). Concentrated ethanolic solutions allow the fabrication of thin films via dip coating. Using UV-irradiation and subsequent moderate temperature treatment compact films of elemental silver can be obtained. The resulting silver films show excellent electrical properties with sheet resistances down to 0.7Ω/sq at a film thickness of 25nm corresponding to a specific electrical resistance of 1.75×10−8Ωm very close to the value of bulk silver. For the potential application in optoelectronic devices, the complex was tested as an ink in a soft printing process for the preparation of patterned silver films.

Assessment of potential causes of falsely positive Mycobacterium tuberculosis breath test

A suite of volatiles have previously been identified as specific markers of Mycobacterium tuberculosis metabolism in vitro. These markers - methyl phenylacetate, methyl p-anisate, methyl nicotinate, o-phenylanisole with the addition of methyl salicylate, may also be derived from other sources and confound development of a breath test for tuberculosis. To identify potential sources of these potential biomarkers food products, cosmetics, TB medication, environmental air and cigarette smoke were analysed for these markers using solid phase microextraction coupled with Gas Chromatography/Mass Spectrometry. Breath from healthy subjects, including smokers was also tested. Methyl salicylate was commonly detected, making this unsuitable as a specific marker for M. tuberculosis. Methyl nicotinate was detected repeatedly in cigarettes. Methyl phenylacetate was detected in 1.7% of healthy subjects and o-phenylanisole in just 1% of healthy breath indicating these may be more suitable for inclusion in the tuberculosis breath test due to their low "background" level. These results justify further clinical studies to further explore these markers as specific indicators of M. tuberculosis infection.

ChemInform Abstract: Aerobic Palladium(II)‐Catalyzed Dehydrogenation of Cyclohexene‐1‐carbonyl Indole Amides: An Indole‐Directed Aromatization.

AbstractIn the presence of O2, PivOH, Pd(OAc)2, and methyl nicotinate cyclohexenes of type (I) and (IV) are found to undergo unexpected aromatization to afford N‐benzoylindoles like (II) and (V).

Electrogenerated N‐Heterocyclic Carbenes in the Room Temperature Parent Ionic Liquid as an Efficient Medium for Transesterification/Acylation Reactions

AbstractN‐Heterocyclic carbenes (NHCs), generated by electrochemical reduction under galvanostatic control of 1,3‐dialkylimidazolium‐based ionic liquids, were employed as catalysts in transesterification reactions in the parent, room temperature ionic liquids (RTILs) as solvents, without the utilisation of any volatile organic solvent or base. The reaction between isopropenyl or ethyl acetate and an alcohol (not efficient in the absence of catalyst) was induced by the presence of an electrogenerated NHC, which seems to assist the proton transfer from the alcohol to the ester, yielding the corresponding acetate. The reaction also proceeds with methyl nicotinate as starting ester and 2‐(diethylamino)ethanol or benzyl alcohol as alcohols and leads to the corresponding biologically active compounds, nicametate and benzyl nicotinate, in good yields. All products were isolated in good to excellent yields and complete recyclability of the ionic liquid as solvent has been demonstrated.

Rational formulation design

To be efficacious and to satisfy the requirements for claim substantiation, a cosmetic formulation must achieve effective targeting of an active in the skin. Although the basic principles governing the skin permeation and disposition of molecules have been known for many years, attention has been far less focused on the role of the vehicle, particularly at cosmetically relevant doses. In this article, we discuss the necessity to understand the fate of the formulation components as well as the active once applied onto skin. Recent data confirm that the residence time of the formulation constituents can have a profound impact on the fate of the active. Approaches to identify the ideal vehicle for skin delivery are considered critically, specifically the recent work on 'formulating for efficacy' (FFE) by the late Johann Wiechers. Essentially, FFE aims to match the active with the optimal vehicle for skin delivery based on matching polarity/solubility values of the trinity of skin, active and vehicle. The emerging importance of techniques that provide insight to how the vehicle distributes in and on skin is highlighted.

Synthesis and structure of five or six-coordinate manganese deuteroporphyrin-niacin dyads with intramolecular axial pyridine

Abstract Deuteroporphyrin-niacin dyads with different chain lengths have been synthesized by modification of the propionate side chains of hemin. When a manganese ion was inserted into the porphyrin core, the UV spectral shift of manganese deuteroporphyrin-niacin dyads were experimentally demonstrated to mainly originate from the intramolecular coordination. In order to elaborate the intramolecular coordination, the spectra of single manganese porphyrin complexes in CH 2 Cl 2 solution were measured and compared to that of the addition of axial ligands (pyridine and methyl nicotinate). Among all the synthetic dyads, the compounds of 2,7,12,18-tetramethyl-13,17-di(3-hydroxypropyl nicotinate) porphyrin and 2,7,12,18-tetramethyl-13,17-di(3-aminoethyl nicotinate) porphyrin manganese bearing the short chains did not show intramolecular coordination of the terminal base on the metal ion. Other three compounds of the niacin moiety indirectly bonded to the propionate side chains of manganese porphyrin through the diols linkage exhibited optical spectra characteristic of five or six-coordinate manganese complexes. These results indicate that the niacin groups' access to the Mn(III) center depended on the chain lengths.

Detection and visualization of intracutaneous allergic type‐specific elements using long‐wavelength near‐infrared hyperspectral imaging

This study aimed to develop a method for the assessment of allergic dermatitis by using the long-wavelength near-infrared spectrum (more than 1000 nm) to detect intracutaneous allergic type-specific elements. Such a method was realized by establishing a spectral classifier for the spectra of type I and type IV allergic dermatitis reactions. Near-infrared spectral images of histamine-induced cutaneous reaction (type I) and contact hypersensitivity erythema elicited by squaric acid dibutylester (SADBE; type IV) were obtained, and the absorption spectra of normal and inflamed skin were extracted from these spectral images. A spectral classifier was established from these training datasets, and it was then applied to two test cases, red flare by methyl nicotinate (normal) and metal allergy (type IV). The spectral classifier established by canonical discriminant analysis (CDA) achieved very accurate detection (normal: 87.67%, type I: 87.00%, type IV: 98.5%). Furthermore, the test cases were also correctly classified: the red flare induced by methyl nicotinate was categorized as normal skin and the metal allergy was categorized as a type IV allergic reaction. These results suggest a possible application of near-infrared spectral imaging to the assessment of allergic dermatitis.

Transition metal mediated synthesis using [11C]CO at low pressure – a simplified method for 11C‐carbonylation

Transition metal mediated carbonylation with [11C]CO has proven a useful method to label a wide array of compounds in the carbonyl position. However, the general use in radiopharmaceutical synthesis has been hampered by the low solubility of carbon monoxide in most solvents and the resulting challenge to confine [11C]CO in low volume reaction vessels. This paper introduces a method that utilises xenon to transfer pre‐concentrated [11C]CO to a sealed disposable glass vial containing carbonylation reagents. The high solubility of xenon in the organic solvent made it possible to confine the [11C]CO without utilising a pressure autoclave or chemical trapping additives. The utility of the method in 11C‐carbonylation was investigated by conducting three model reactions, where [11C‐carbonyl]N‐benzylbenzamide, [11C‐carbonyl]triclocarban and [11C‐carbonyl]methyl nicotinate were afforded in decay corrected radiochemical yields of 71 ± 6%, 42 ± 15% and 29 ± 10%, respectively. These promising results and the straight forward technical implementation suggest that 11C‐cabonylation can become a viable mean to provide labelled carbonyl functionalities in routine radiopharmaceutical synthesis. Compounds labelled with short lived positron emitters are used in Positron Emission Tomography, a molecular imaging technology with applications in clinical diagnostics, clinical research and basic biomedical research.

Photoactivatable Organometallic Pyridyl Ruthenium(II) Arene Complexes

The synthesis and characterization of a family of piano-stool RuII arene complexes of the type [(η6-arene)Ru(N,N′)(L)][PF6]2, where arene is p-cymene (p-cym), hexamethylbenzene (hmb), or indane (ind), N,N′ is 2,2′-bipyrimidine (bpm), 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendio), or 4,7-diphenyl-1,10-phenanthroline (bathophen), and L is pyridine (Py), 4-methylpyridine (4-MePy), 4-methoxypyridine (4-MeOPy), 4,4′-bipyridine (4,4′-bpy), 4-phenylpyridine (4-PhPy), 4-benzylpyridine (4-BzPy), 1,2,4-triazole (trz), 3-acetylpyridine (3-AcPy), nicotinamide (NA), or methyl nicotinate (MN), are reported, including the X-ray crystal structures of [(η6-p-cym)Ru(bpm)(4-MePy)]2+ (2), [(η6-p-cym)Ru(bpm)(4-BzPy)]2+ (6), [(η6-p-cym)Ru(bpm)(trz)]2+ (7), [(η6-p-cym)Ru(phen)(Py)]2+ (10), and [(η6-ind)Ru(bpy)(Py)]2+ (13). These complexes can selectively photodissociate the monodentate ligand (L) when excited with UVA or white light, allowing strict control of the formation of the reactive aqua species [(η...