Histamine release by some new skeletal muscle relaxants studied at the rat ileum.
The effects of 6 non-depolarizing muscle relaxants on histamine release were investigated, pharmacologically, using histamine and histamine antagonists, e.g. mepyramine, clemastine, dimotane. The results showed that gallamine, pancuronium, vecuronium, atracurium, tubocurarine and alcuronium produced concentration-dependent contractions in the rat ileum, gallamine and pancuronium being the most effective agents in producing muscle contraction. The H1 blocker, mepyramine, reduced the contractions produced by the muscle relaxants, as well as that produced by histamine. However, there was always some residual contraction, not blocked by high concentrations of mepyramine in the case of the muscle relaxants, but not in the case of histamine, the contraction of which was totally blocked by high concentrations of mepyramine. These results also suggested that, in part, the contraction produced by muscle relaxants, may be due to a mechanism other than histamine release, e.g. release of other mediators and/or an effect on intracellular calcium ions. Since very high concentrations of atracurium and vecuronium (40-50 times higher than clinical concentrations) were used in this study to produce marked contractions, the implication is that in clinical concentrations, they have little effect on histamine release. In contrast, gallamine and pancuronium can release histamine even at low concentrations, i.e. at or near their clinical concentrations in man. These, therefore, are the cause of the adverse reactions seen after drug administration.
Anaesthetics Unit, London Hospital Medical College, Whitechapel, England.
F A
FA
Wali
A
A
Hayter
E
E
Greenidge
V
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Makinde
D000818:Animals; D001279:Atracurium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000378:metabolism* / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009994:Osmolar Concentration; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009466:Neuromuscular Blocking Agents; D001279:Atracurium; D006632:Histamine; D011738:Pyrilamine