All muscle relaxants inhibit histamineN-methyltransferasein vitro, but vecuronium, a steroid-derived muscle relaxant, is the most potent inhibitor. It has been suggested that administration of vecuronium prior to giving a drug that releases histamine may exaggerate the hemodynamic or vascular effects. Volunteers were injected intradermally with 5×10−4M concentrations of histamine, and the combination of vecuronium and histamine, to evaluate thein vivo significance. Vecuronium did not alter the measured wheal and flare responses to injected histamine at 5, 15, 30, 40, 50 and 60 mins. There is no evidence that inhibition of histamineN-methyltransferasein vivo will alter the vascular effects of histamine.

Chemically and pharmacologically unrelated molecules release histamine in humans to produce both cutaneous and systemic responses. It has been suggested that molecular changes in the new benzylisoquinoline-derived muscle relaxant, atracurium, make it less likely to cause histamine release. We therefore injected volunteers intradermally with equimolar concentrations of various muscle relaxants, morphine, papaverine (a benzylisoquinoline), and histamine, to evaluate the relative ability of these drugs to cause wheal and flare responses, and mast-cell degranulation. There were no significant differences in wheal and flare responses among the three benzylisoquinoline-derived muscle relaxants, D-tubo-curarine, metocurine, and atracurium. The cutaneous effects of morphine were significantly greater than those of the benzylisoquinoline muscle relaxants, suggesting both direct vascular changes and histamine release. Papaverine injection was followed by a significant wheal but no flare. Skin biopsies from vecuronium- and papaverine-induced wheals revealed normal intact mast-cell granules, suggesting a direct cutaneous vascular response rather than histamine release. Skin biopsies after morphine and atracurium injections revealed mast-cell degranulation. All evaluated benzylisoquinoline muscle relaxants are equipotent histamine releasers at equimolar concentrations. A hydrogenated, benzylisoquinoline-nitrogen-containing ring, present in atracurium but not in papaverine, appears to be the molecular conformation responsible for mast-cell degranulation by atracurium.