Curariform Activity Research Articles

Erythrina Americana Miller (“Colorín”; Fabaceae), a versatile resource from Mexico: A Review

We present a review of published and unpublished information on the multipurpose tropical legume tree, Erythrina americana. The genusErythrina (Fabaceae) consists of 115 species distributed throughout the tropical regions of the world; 25 species are known from Mexico. E. americana is used as an ornamental tree, also as shade for cocoa and coffee and as a support tree, as a live fence, and for green manure and animal feed. The flowers are frequently eaten, used to make tea and as a sedative. The seeds are toxic because of alkaloids; they are applied in folk medicine as laxative, diuretic, expectorant, anti-asthmatic and antimalarial. The first compounds isolated were isoquinoline alkaloids; of these, β-erythroidine and its more potent derivate dihydro-β-erythroidine were shown to possess curariform activity. Of both compounds, the LD50 has been evaluated, and their effects on the central nervous system have been studied. These studies confirmed some applications in popular medicine.

Cyclobutanedicarboxylic acids IX. Salts of bis(dialkylaminoalkylamides) of α-truxillic acid with curariform activity

Cyclobutanedicarboxylic acids IX. Salts of bis(dialkylaminoalkylamides) of α-truxillic acid with curariform activity

Cyclobutanedicarboxylic acids. VIII. Synthesis and curariform activity of bisquaternary salts of α- truxillic acid ω-dialkylaminoalkylamides

Cyclobutanedicarboxylic acids. VIII. Synthesis and curariform activity of bisquaternary salts of α- truxillic acid ω-dialkylaminoalkylamides

Synthesis and curariform activity of p,p″-bisquaternary ammonium derivatives of p-terphenyl

Synthesis and curariform activity of p,p″-bisquaternary ammonium derivatives of p-terphenyl

Curariform activity of some δ-dimethylaminobutyl ester methiodides

Curariform activity of some δ-dimethylaminobutyl ester methiodides

Synthesis of a bifunctional coordination complex of osmium with curariform activity.

Based on the known curariform action of tris(bipyridyl)iron(II) sulfate and other complex ions, two series of bifunctional ligands designed to hold transition metal ions at approximately the same distance apart as the interquaternary ammonium distance in the potent neuromuscular block agents were synthesized. In the first series two 1,10-phenanthrolines (R1) were joined at the 2 position to form four compounds: R1CO-c-N(CH2CH2)2N-COR1, R1CONH-1,2-C6H10-NHCOR1, R1CONH-1,2-C6H4-NHCOR1, and R1CON(CH3)(CH2)2N(CH3)COR1. In the second series two terpyridines (R1) were joined by different chains to give R2(CH2)2CH=CH(CH2)2R2, R2CH2C(CH3)(OH)(CH2)2C(CH23)(OH)CH2R2, R2CH2C(CH3)(OH)C(CH3)(OH)CH2R2, and R2CH2(OH)-1,4-C6H10-(OH)CH2R2. Three other ligands in which the terpyridines were joined by 5-, 60, and 7-methylene groups were also made. The ligands were converted to nickel(II) complexes and the coordination of each nickel ion was completed by adding terpyridine. These were assayed by the intravenous mouse LD50 method. The most potent ligand, the di-hydroxy compound R2CH2(OH)-1,4-C6H10-(OH)CH2R2 was then converted to the bis(pyridinebipyridine)diosmium-(II) coordinated complex and assayed by the iv mouse LD50 method and by the ED50 isolated guinea-pig diaphragm method. By the iv mouse LD50 method, it was about twice as potent as d-tubocurarine and by the isolated diaphragm method, it was 16 times more potent. The compound has been called dihydroxyosmarine tetrachloride or DHO for short. The term "transarine" ions is proposed for transition metal coordination complexes having curariform action. The position of the transarine ions is discussed in the classification of cholinergic ligands, in structure-action relationships, and in relation to some current ideas on receptor mechanisms.

Neuromuscular blocking agents: Structure and activity

Correlation of crystal structure analyses and model building of rigid molecules indicate the structural requirements for curariform activity and the structural differences between depolarizing and non-depolarizing neuromuscular blocking agents.

Diterpene alkaloids. Isolation and study of two new alkaloids.

Abstract Two new alkaloids tentatively named as “denudatine” and “denudatidine” have been isolated in pure form from an indigenous crude drug “Judwar” which has been provisionally identified as the roots of Delphinium denudatum Wall. (Fam. Ranunculaceae). The purity of these alkaloids has been checked by paper chromatographic analysis and they have been characterised. Denudatine is the major alkaloid and has been isolated in pure form in a yield of 0.05 per cent. On the basis of microanalysis for the elements of the base, m.p. 248–249° and its derivatives; the determination of the active hydrogen, =N–Me, ≡C–Me and infra-red and ultra-violet absorption spectra, denudatine has been tentatively classified as a diterpene alkaloid of atisine group. Pharmacological actions of denudatine have been investigated. The normal rhythmic contractions of isolated rabbit duodenal strip are inhibited. The isolated guinea-pig uterine strip is stimulated by the base solution. It decreases the tone and inhibits the peristaltic movements of the intestine but does not show any effect on the blood pressure and respiration of the anaesthetised dog. It is non-toxic and lacks curariform activity. Denudatidine, m.p. 273° (yield, 0.003 per cent) has not been studied further.

Condensation of Dialdehydes with Reissert Compounds. Synthesis of a Compound Having Curariform Activity

Condensation of Dialdehydes with Reissert Compounds. Synthesis of a Compound Having Curariform Activity

Quaternary Ammonium Salts of 8-(Dialkylaminoalkox y)-theobromines and -caffeines as Curariform Agents

Three 8-(dialkylaminoalkoxy)-theobromine compounds were prepared by reacting the appropriate sodium dialkylamino alcoholate with 8-chlorotheobromine. Nine quaternary salts were prepared from the above three compounds by reacting each with methyl iodide, ethyl iodide, and benzyl chloride. The nine quaternary compounds along with nine corresponding caffeine quaternary compounds, previously reported, were tested for their curariform activity.

Synthesis of Quinolizine Derivatives. IX. Synthesis of 3, 3'-Polymethylenediquinolizidine

In expectation of a curariform activity with little side effects, methiodide of 3, 3'-polymethylenediquinolizidines (I : n=4, 6, 8, and 10) were synthesized. Condensation of the potassium salt of 3-ethoxycarbony1-4-oxoquinolizidine and polymethylene bromide, followed by saponification and decarboxylation, and reduction with lithium aluminum hydride of the lactam compound so obtained afforded the objective compounds (I). (I : n=4) was also obtained through 3-(4-phenoxybutyl) quinolizidine (IX) as an intermediate and compounds obtained by the two procedures were found to be identical. The curariform activity of (I) (n=4 and 6) was one-quarter that of tubocurarine chloride while their toxicity was 6 and 10 times, respectively, of tubocurarine. The compound with n=10 had a strong antibacterial and antifungal activity.

Effect of inorganic complex ions on transmission at a neuromuscular junction.

SOME aspects of the chemical and biological activity of the inorganic complex ions have been previously reported by Beccari1 and by Dwyer and co-workers2–4. These workers have indicated that the complex cations show extremely high chemical stability, and most probably pass through the body unchanged. They also exhibit marked biological activity4, and when injected intraperitoneally into mice2 cause paralysis and death by respiratory failure suggestive of curariform activity. We have investigated their pharmacological mode of action on the rat diaphragm–phrenic nerve and toad (Bufo marinus) rectus abdominis muscle preparations. Investigations have also been carried out, in collaboration with Dr. Rosamond M. Eccles, of the Department of Physiology, Australian National University, using the toad sartorius nerve–muscle preparation and the isolated superior cervical ganglion of the rabbit.

Quaternary Salts of 2,4,6-(Dialkylaminoalkoxy)-1,3,5-Triazines and 2, 4-(Dialkylaminoalkoxy)-Quinazolines as Curare Agents

Three 2,4,6-(dialkylaminoalkoxy)-1,3,5-triazines, two 2,4-(dialkylaminoalkoxy)-quinazolines, seven tris quaternar salts of the triazines and three bis quaternary salts of the quinazolines were prepared and identified. Seven of the quaternary salts were tested for curariform activity by the mouse screen-drop test and the rabbit head-drop test. In the chick, the quaternary salts produced a flaccid paralysis associated with a pachycurare-type block. Of the seven compounds tested, six were appreciably less active than Flaxedil®. One compound, the tribenzchloride of 2,4,6-(β-diethyl-aminoethoxy)-1,3,5-triazine, was approximately twice as active as Flaxedil® in the mouse and seven times as active in the rabbit.

Curare-Like Activity of Some Bis-Fluorenyl-Bis-Quaternary Ammonium Compounds

1. The curariform activity of a new series of bis-quaternary ammonium compounds is reported. 2. Moderate increase of activity is obtained by shortening the distance between nitrogen atoms from approximately 15 Å to 9 Å. 3. Replacement of N-ethyl groups with N-methyl in the 6-carbon chain analog decreases both the activity and the subcutaneous absorption in mice, but has no effect on the activity as measured in dogs and rabbits.

CURARE-LIKE ACTION OF MAGNOCURARINE ISOLATED FROM MAGNOLIA OBOVATA

On the pharmacological investigation of principal constituents of magnoliaceous plants growing in Japan, there are no scientific reports except that of Sasaki (1). He succeeded in separating some substances, in a laquer-like state, which possess curariform activity, from the alcoholic extracts of a few plants of this family, including Magnolia obovata, Thunb. From the bark of Magnolia obovata Thunb. (Japanese name “Hohnoki”) Tomita and Inubushi (2) have recently isolated a new alkaloid, named it magnocurarine and determined its chemical structure. It was found to be N-methyl coclaurine `methyl hydroxide, which resembles one half of the molecular structure of d-tubocurarine (see Fig. 1). Magnocurarine is almost colorless, microscopic, prismatic crystals, melting at 200°C with effervescence and is readily soluble in water, but insoluble in most of organic solvents. We have decided to study in some detail the properties of magnocurarine chloride (MC) and compared the curare-like action of this substance with that of d-tubocurarine chloride (TC) and of decamethonium iodide (C10). We had planned the comparative studies of the curare-like action of MC and TC but because of the lack of TC we have been compelled to use C10 instead of TC in some experiments.

Curariform Activity and Chemical Structure. VIII. Lactones Derived from Quinolizidine1,2

Curariform Activity and Chemical Structure. VIII. Lactones Derived from Quinolizidine^1,2

Curariform Activity and Chemical Structure. VI. Syntheses in the β- and γ-Carboline Series1,2

Curariform Activity and Chemical Structure. VI. Syntheses in the β- and γ-Carboline Series^1,2

Curariform Activity and Chemical Structure. VII. Some 1-Skatylisoquinoline Derivatives and a Novel Method for their Synthesis1,2

Curariform Activity and Chemical Structure. VII. Some 1-Skatylisoquinoline Derivatives and a Novel Method for their Synthesis^1,2

The curariform activity of the menispermaceous alkaloids.

Die verschiedenen chemisch charakterisierten Alkaloide, die in Menispermazeen angetroffen werden, sind auf allfallig nutzliche Curarewirkung hin untersucht worden. Blos diejenigen Verbindungen mit Dibenzyltetrahydroisochinolinstruktur, die zwei Stickstoffatome mit je vier Kovalenzen und eine Elektrovalenz besitzen bzw. in solche Verbindungen umgewandelt werden konnen, besitzen eine nennenswerte Wirkung.

Curariform Activity and Chemical Structure. V.1 Syntheses in the Quinolizidine Series2

Curariform Activity and Chemical Structure. V.¹ Syntheses in the Quinolizidine Series²