Abstract
The hypothesis that histamine H2 receptor blockade adversely affects neuromuscular function was tested, in vivo, in rats anaesthetised with urethane during mechanical pulmonary ventilation. Succinylcholine was administered as a bolus and constant-rate infusion to maintain 49.2% (±1.5 SEM) twitch suppression in 19 rats. Cimetidine iv, 3.2, 7.5, 10, 17.8, 23.7, 31.6, or 56.2 mg ·kg−1 was then administered in groups of two to three rats. Cimetidine produced an immediate potentiation of twitch suppression followed by a transient reversal and then a continued potentiation. Peak potentiation occurred within 19.0 (±2.7) sec and was maintained in 11 rats at steady-state. Reversal was evident 4.1 (±0.4) min after cimetidine administration. There was a good relationship between peak potentiation and serum cimetidine concentration with 50% potentiation occurring at 46.5 (±4.6) μg ·ml−1. Potentiation at steady-state was not correlated to serum cimetidine concentration but there was a weak relationship between reversal and serum cimetidine concentration. These results support reports from patients of an interaction between cimetidine and succinylcholine.
Résumé
L’hypothèse voulant que le blocage de récepteurs histaminiques de type H2 affecte la fonction neuromusculaire a été vérifiée in vivo sur des rats anesthesies avec de l’uréthane et ventilés artificiellement. Chez 19 rats, un bolus de succinylcholine suivi d’une perfusion constante ont été administrés de façon à maintenir une dépression du «twitch» de 49,2% (±1,5 SEM). Chez des groupes deux ou trois rats, de la cimétidine a alors été administrée par voie intraveineuse à raison de 3,2, 7,5, 10, 17,8, 23.7, 31,6, ou 56,2 mg ·kg−1. La cimétidine a produit une potentialisation immédiate de la dépression du «twitch» suivie d’une récupération transitoire puis d’une potentialisation soutenue. La potentialisation maximale est survenue en 19,0 (±2,7) sec et s’est maintenue à un niveau stable chez 11 rats. La récupération était évidente 4,1 (±0,4) min après l’administration de cimétidine. Il y avait une bonne relation entre la potentialisation maximale et la concentration sérique de cimétidine avec une potentialisation de 50% survenant à 46,5 (±4,6) μg ·ml−1. Le degre de potentialisation soutenue à un niveau stable n’était pas corrélatif à la concentration sérique de cimétidine mais il y avait une faible relation entre la récupération et la concentration sérique de cimétidine. Ces résultats supportent les rapports d’une interaction entre la cimétidine et la succinylcholine chez les humains.
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This project was supported in part by financial assistance from the Pharmacy Research Trust of New South Wales.
An erratum to this article is available at http://dx.doi.org/10.1007/BF03008308.
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Mishra, Y., Ramzan, I. Interaction between succinylcholine and cimetidine in rats. Can J Anaesth 39, 370–374 (1992). https://doi.org/10.1007/BF03009048
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DOI: https://doi.org/10.1007/BF03009048