Alloferin

D Alloferin Amp. (Roche) GB Alloferin (Roche) wfm USA Alloferin (Roche) wfm... 

Rowley RW. Hypersensitivity reaction to diaUyl nortoxifer-ine (Alloferine). Anaesth Intensive Care 1975 3 74. 

The same condensation proceeds between two molecules of N j-allyl-Wieland-Gumlich aldehyde (40) to give the so-called alloferine (41), which is important clinically. 

In contrast to this, alcuronium [= alloferine, (41)] may be used for short operations. Initial intravenous doses of 5—10 mg produce paralysis for 15—20 minutes, and repetitive doses of 2—5 mg may be given. No undesired side-effects have been described and alcuronium is now widely used by anaesthetists. ... 

Dichloride, C H CIjNjOj, N,N -diallylnortoxiferinium dichloride, Ro 4-3816, Alloferin, Toxiferene, Crystals from methanol or ethanol. Compd contains 5 moles of water of crystn after equilibration in air [ ]p —348 (methanol) uv max (methanol) 292 nm (e 43,000k... 

Activity C-T. 1 is probably the most effective peripheral muscle relaxant. It is hardly used in current therapy because the corresponding diallylnortoxiferinium chloride (alcuronium chloride, Alloferin ) has a shorter duration of action. The muscle relaxant effect results from a (competitive) expulsion of acetylcholine from the receptors of the motoric endplates with paralysis of the transversely striated musculature (overdoses cause death by asphyxiation). 

Generally speaking, all the muscle relaxants discussed here have been reported to produce histamine release when injected intravenously (i.v.). This was shown by an increase in plasma histamine level (Lorenz et al. 1972). The frequency of reaction (significant increase in plasma histamine) was highest with suxamethonium (3 of 8 volunters), followed by alcuronium (alloferin, 2 of 8), and then pancuronium (1 of 7) (Lorenz and Doenicke 1978). However, the latter authors found a poor correlation between the increase in plasma histamine levels and the incidence of clinical manifestations, e.g., such manifestations were more frequent with pancuronium than with suxamethonium. These above findings contradict the low incidence of acute (anaphylactic-like) reactions to pancuronium in practice. 

Pharmacology. C.a. interrupt nervous impulses at the end plates of motor nerves by displacing acetylcholine, leading to paralysis of striated muscles. Pharmacological effects are manifested only after injection (arrow or syringe). Because Ca. are absorbed very slowly from the intestine, animals killed by arrow poisons can be eaten with impunity. C.a. are used clinically as muscle relaxants in operations, and to relieve severe tetanus and nervous muscle cramps. Since the natural preparations vary in composition, and have unpleasant side effects, the pure alkaloids or synthetic or semisynthetic analogs (e.g. Alloferin) are used in modern medicine. 

Fig. 84. Autoradiograph (A) and fluorogram (B) of two thin-layer chromatograms of H-labelled diallylnortoxi ferine ( H-alloferine) [408]. Layers A. silica gel G B, silica gel G and anthracene (50 + 50) (g/g). Solvent acetonitrile - hexane - diethy-lamine (75.5 -f 17.5 -f 5). Film Eastman Kodak Ko-direx contact time 18 h at —70° C...

Somewhat later than (H-)-tubocurarine and following the studies of Stry-chnos curare alkaloids, toxiferine underwent clinical trials and was found to be rather more potent and fairly free from side effects, but its very long duration of action and its instability in solution precluded clinical exploitation of the alkaloid (485). However, modification of the toxiferine molecule by replacing the two iVb-methyl groups with JVb-allyl functions produced the semisynthetic compound alcuronium (4g), or Alloferin (267, 508), which is still in use as a short-lasting muscle-relaxant in minor surgery. It is obtained by semisynthesis from strychnine via Wieland-Gumlich aldehyde and subsequent quaternization with allyl bromide. See further. Bowman (485 pp. 139-140). 

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