Lappaconitine Hydrobromide Research Articles

Crystal Structure Analysis and Antinociceptive Property of Lappaconitine Hydrochloride

An alkaloid compound, lappaconitine Hydrochloride, was synthesized with lappaconitine which was isolated from the root ofAconitum sinomontanum Nakaiin Gansu province in China. The structures were elucidated by IR,NMR, Anal. and X-ray diffraction analysis. Crystal data: C32H47ClN2O9,Mr= 639.17, space group monoclinic, P21; a=10.665 (7) Å, b=12.178 (7) Å and c=12.214 (7) Å; β=91.003 (10)°, Z=2, Dx= 1.338 mg/m-3,F(000)= 684,µ=0.18.00 mm-1, V=1586.1 (16) Å3; R1=0.038,wR2=0.087, Flack parameter x= -0.12 (7). RingA, B, C, D, EandFrespectively present boat, chair, envelope, boat, boat and envelope forms. The absolute configuration was determined as 1S, 4S, 5S, 7S, 8S, 9S, 10S, 11S, 13R, 14S, 16S, 17 R. And the analgesic potential has been investigated in a mouse model of acute pain. The result exhibited that the analgesic effect of the compound is worse than lappaconitine hydrobromide.

X-ray structure analysis of lappaconitine

Lappaconitine is an important alkaloid of the aconite family and its biological activity is closely related to its structure. Through an X-ray structure analysis of hydrated lappaconitine hydrobromide, which was synthesised by us through a new method, the absolute configuration of lappaconitine was determined: monoclinic, P2 1 , a = 10.619(2) Å, b = 12.196(3) Å, c = 12.282(2) Å, β = 90.87(1)° and Z = 2; Flack parameter is −0.0083(0.0046) and S = 0.867. Rings A, B, C, D, E and F, respectively, present boat, chair, envelope, boat, boat and envelope forms. The absolute stereo configuration of lappaconitine was determined as 1S, 4S, 5S, 7S, 8S, 9S, 10S, 11S, 13R, 14S, 16S and 17R.

Complexation of Lappaconitine with Glycyrrhizic Acid: Stability and Reactivity Studies

NMR and UV-vis spectroscopy have been used to study the complexation of antiarrhythmic alkaloid lappaconitine with an efficient complexing agent from licorice, glycyrrhizic acid, which is known to profoundly influence the therapeutic activity of the alkaloid in the complex. In MeOH, DMSO, or aqueous solutions, lappaconitine has been shown to form a stable complex with glycyrrhizic acid with 1:1 stoichiometry over a broad concentration range from 1 microM to 300 microM. The stability constant K(11) equals 2.0 x 10(5) M(-1) in aqueous solution. A similar complex of lappaconitine hydrobromide--the pharmaceutical formulation used in the treatment of arrhythmia--is 2 orders of magnitude less stable than pure lappaconitine. A notable decrease in the rate of the photoinduced electron-transfer reaction between lappaconitine in a complex with glycyrrhizic acid and tyrosine allows the suggestion of an explicit interrelation between the suppressed chemical reactivity of the bound alkaloid and the changes of its therapeutic efficiency.

Thermochemistry of Lappaconitine Hydrobromide and Its Analogues

Isothermal calorimetry was applied to study the heats of dissolution of lappaconitine hydrobromide at varied dilution. The data obtained were used to calculate the standard enthalpy of dissolution of C32H44N2O8 · HBr in an infinitely diluted (standard) aqueous solution. The heats of combustion and melting of C32H44N2O8 · HBr were calculated using approximate methods. A combination of experimental and calculation techniques was used to find the standard heats of formation of lappaconitine hydrobromide and its 33 analogues.

Diterpenoid alkaloids as a new class of antiarrhythmic agents. Structure-activity relationship

The cardiotropic activities of 111 diterpene alkaloids and their synthetic derivatives having lycoctine, heteratisine, napelline, and denudatine skeletons have been studied. It has been established that the overwhelming majority of these compounds exhibit a pronounced antiarrhythmic and antifibrillatory action, which is a finding of practical interest. Their structure-activity relationships — the directions of their action in relation to the results of x-ray structural analysis — have been investigated. The following have been selected and proposed as antiarrhythmic agents for practical medicine: lappaconitine, deacetyllappaconitine, 6-benzoylheteratisine, 14-benzoyl talatisamine, 1-benzoylnapelline, and others. Of them, lappaconitine hydrobromide (allapinin) has been introduced into public health practice.

Studies on the metabolism of lappaconitine in humans. Identification of the metabolites of lappaconitine in human urine by high performance liquid chromatography

The metabolites of lappaconitine in the urine of humans having been previously administered intramuscularly with lappaconitine hydrobromide were studied using high performance liquid chromatography with electrochemical and ultraviolet detection. The urine was extracted by means of liquid- and solid-phase extractions. Each of the metabolites of lappaconitine was purified by high performance liquid chromatography on a reversed phase column and identified on the basis of the chromatographic behaviour and the detector response. It was proved that lappaconitine, N-deacetyl-16-O-demethyllappaconitine and N-deacetyllappaconitine were excreted in urine from humans receiving lappaconitine.

Separation and characterization of the metabolic products of lappaconitine in rat urine by high-performance liquid chromatography

The separation and characterization of the metabolic products of lappaconitine in rat urine by high-performance liquid chromatography with electrochemical and ultraviolet detection are described. urine samples from rats intravenously administered lappaconitine hydrobromide were extracted with chloroform and then purified on a Sep-Pak C 18 cartridge. The subsequent resolution into individual compounds was achieved by high-performance liquid chromatography. Identification of these compounds was based on comparisons of the chromatographic behaviour and the detector response with those of authentic samples. Changes in the ratio of lappaconitine to its metabolites in rat urine with time after dosing led to a proposal for one of the probable metabolic pathways of lappaconitine in the rat.

Method of obtaining allapinine from the epigeal part of Aconitum leucostomum

The industrial processes for obtaining allapinine (lappaconitine hydrobromide) from the epigeal part ofAconitum leucostomum have been studied. As a result, a rational method of obtaining allapinine from the plant raw material has been developed which consists in the extraction of the raw material with 80% ethanol and concentration to an aqueous residue, followed by extraction with chloroform, purification, the production of technical allapinine, and its recrystallization from methanol or from aqueous ethanol. The yield of allapinine satisfying the requirements of VFS 31-1667-86 amounts to 72–80% of its amount in the raw material.