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IN VITRO TIME COURSE STUDIES ON TRAIN‐OF‐FOUR FADE INDUCED BY HEXAMETHONIUM, PANCURONIUM AND DECAMETHONIUM IN THE RAT HEMIDIAPHRAGM
Author(s) -
Gwee M. C. E.,
Cheah L. S.
Publication year - 1989
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1989.tb02400.x
Subject(s) - decamethonium , hexamethonium , medicine , anesthesia , chemistry , receptor , atropine
SUMMARY 1. In vitro time course studies on the effects of hexamethonium (7 mmol/L), pancuronium (5 μmol/L) and decamethonium (220 μmol/L) on nerve‐evoked (2 Hz for 2 s every 20 s) maximal twitches (T 1 , T 2 , T 3 , T 4 ) of the rat hemidiaphragm were conducted. All three drugs progressively depressed all four twitches in a given train but at different rates (T 4 > T 3 > T 2 ≫ T 1 ). 2. The response‐time profiles for T 1 and T 4 varied widely for the three drugs such that, for the same degree of T 1 ‐block, each drug produced a different magnitude of T 4 ‐block during the onset of and recovery from neuromuscular blockade. 3. Analysis of the T 1 versus T 4 /T 1 plot showed that, at 50% T 1 ‐block, the corresponding T 4 /T 1 (i.e. train‐of‐four ratios) during the onset (and recovery) phase were 0.16 (0.29), 0.46 (0.40) and 0.66 (0.53) for hexamethonium, pancuronium and decamethonium, respectively. Thus, for the same degree (i.e. 50%) of twitch (T 1 ) tension depression, the three drugs differed widely in their ability (hexamethonium ≫ pancuronium > decamethonium) to produce fade as reflected in the respective train‐of‐four ratio. 4. Our results therefore show that the train‐of‐four ratio (T 4 /T 1 ) at 50% T 1 ‐block obtained from such in vitro time course studies is a useful quantitative index of the potential of various drugs to cause train‐of‐four fade. Based on this index a classification of various compounds already studied is proposed as follows: hexamethonium ≫ pancuronium ∼ (+)‐tubocurarine > decamethonium ∼ succinylcholine ≫α‐bungarotoxin.