Summary
The decamethonium blood concentration pattern following intravenous injection of C14 labelled C10 is characterized by two well-distinguished peaks, the first occurring at the time of injection, and the second after variable periods of time, depending on the dosage employed. Thus, the second peak was found to shift from 20-30 min. after injection when the administered dose was increased from 1.8 to 3.0 mg./kg., its time of onset fairly closely coinciding with the initial stage of decurarization, as shown by parallel experiments using graphic recording of faradically stimulated masseter contractions. Based on these findings, and from previous studies by the same workers, an attempt was made to elucidate the causes for the unusual behaviour of C10 as compared to d-tubocurarine—the latter, as is well known, exhibiting a simple elimination curve with but one initial peak followed by gradual decrease of blood concentration levels.
Pre-treatment with a large dose of non-labelled decamethonium (5 mg./kg.) results in disappearance of the second peak, which is replaced by an extended “plateau,” whereas pre-treatment with 100 mg./kg. d-tubocurarine causes displacement of both peaks towards the right. The evidence thus substantiates the authors’ previously suggested opinion that the initial drop of decamethonium blood levels is associated with its fixation by muscle receptors, and that the second peak, corresponding to the decurarization stage, is due to re-introduction of either inactivated decamethonium or its radioactive degradation products from the muscles into the bloodstream.
Finally, the identity of receptors for decamethonium and d-tubocurarine is discussed.
Résumé
La courbe de la concentration sanguine au décamethonium a la suite de l’injection intraveineuse de C14 marque C10 est caracterisee par deux pics bien distincts le premier survenant immediatement apres l’injection, et le deuxieme apres des délais variables selon la dose employée. Ainsi, nous avons réalisé que le deuxieme pic se déplace de 20 a 30 minutes aprés l’injection, lorsque nous augmentons la dose de 1.8 a 3.0 mg./kg.; le moment de son debut coincide a tres peu pres avec la phase inltiale de decurarisation, comme le prouvent des experiences paralleles ou l’on a fait un graphique des contractions des masseters stimulés par un courant faradique. Forts de ces donnees et a la suite d’autres etudes par les auteurs, nous avons etudie les causes des effets differents du C10 et de la d-tubocurarine, cette derniere, on le sait, donne une courbe d’élimjnation ordinaire ne montrant qu’un pic suivi d’une diminution graduelle des taux de concentration dans le sang.
Un traitement préalable avec une grosse dose de decamethonium non marqu (5 mg./kg.) a entraine la disparition du deuxieme pic a été remplacé par un plateau prolongé, alors qu’un traitement prealable avec 100 mg./kg. de cj-tubocurarine a entraine le deplacement des deux pics vers la droite.
Ces faits confirment l’opinion emise au prealable par les auteurs que la premiere diminution des taux décaméthonium dans le sang est liée á sa fixation par les recepteurs musculaires, et, que le second pic, survenant a la phase de décurarisation, est du a l’apparition dans le courant sanguin soit du decamethonium inactive, soit de ses produits radioactifs degrades par les muscles.
Finalement, nous discutons de l’identite de recepteurs pour le decamethonium et la d-tubocurarine.
Article PDF
Similar content being viewed by others
References
Bovet-Nitti, F. Degradazione di alcune sostanze curarizzanti per azione della colinesterasi. Rendic. 1st. Super. San.12: 138 (1949).
Whittaker, V. P., &Wijesundera, S. The Hydrblysis of Succinyldicholine by Cholisterase. Biochem. J.52: 475 (1952).
Evans, F. T.;Gray, W. S.;Lehmann, H.; &Silk, E. Sensitivity to Succinylcholine in Relation to Serumcholinesterase. Lanceti: 1229 (1952).
Fraser, P. J. Hydrolysis of Succinylcholine Salts. Brit. J. Pharmacol.9: 429 (1954).
Wolleman, M. On the Effect of a Muscle-Relaxing Compound: Succinylcholine. Atti XI° Congr. Soc. It. di Anestesiologia I.T.E., Venezia (1959).
Gray, T. Farmaci depolarizzanti in anestesia. Rec. Prog. Med.2: 141 (1955).
Paton, W., &Zaimis, E. The Pharmacological Actions of Polymethylammonium Salts. Brit. J. Pharmacol.4: 381 (1949).
Zaimis, E. The Synthesis of Methonium Compounds, Their Isolation from Urine and Their Photometric Determination. Brit. J. Pharmacol.5: 424 (1950).
Giovanella, B., Manni, C., &Moricca, G. Turbidimetric Detection of Decamethonium. Experientia15: 393 (1959).
Manni, C.;Moricca, G.;Giovanella, B.; &Mazzoni, P. Studio sul destino di alcuni miorilassanti mediahte l’impiego di composti marcati con isotopi radioattivi. Distribuzione del decametonio marcato con C14. Atti XI° Congr. Soc. It. di Anestesiologia I.T.E., Venezia (1959).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Giovanella, B., Manni, C., Maifzoni, P. et al. Experimental studies on the fate of decamethontium. Can. Anaes. Soc. J. 8, 458–467 (1961). https://doi.org/10.1007/BF03021371
Issue Date:
DOI: https://doi.org/10.1007/BF03021371