In vitro time course studies on train-of-four fade induced by hexamethonium, pancuronium and decamethonium in the rat hemidiaphragm

• Published in: Clinical and experimental pharmacology & physiology Vol. 16; no. 12; p. 897
• Main Authors: Gwee, M C, Cheah, L S
• Format: Journal Article
• Language: English
• Published: Australia 01.12.1989
• Subjects: Animals; Decamethonium Compounds - pharmacology; Diaphragm - drug effects; Diaphragm - physiology; Electric Stimulation; Female; Hexamethonium Compounds - pharmacology; In Vitro Techniques; Male; Muscle Contraction - drug effects; Pancuronium - pharmacology; Rats; Rats, Inbred Strains; Respiratory Muscles - drug effects; Respiratory Muscles - physiology
• ISSN: 0305-1870
• DOI: 10.1111/j.1440-1681.1989.tb02400.x

1. In vitro time course studies on the effects of hexamethonium (7 mmol/L), pancuronium (5 mumol/L) and decamethonium (220 mumol/L) on nerve-evoked (2 Hz for 2 s every 20 s) maximal twitches (T1, T2, T3, T4) of the rat hemidiaphragm were conducted. All three drugs progressively depressed all four twitches in a given train but at different rates (T4 greater than T3 greater than T2 much greater than T1). 2. The response-time profiles for T1 and T4 varied widely for the three drugs such that, for the same degree of T1-block, each drug produced a different magnitude of T4-block during the onset of and recovery from neuromuscular blockade. 3. Analysis of the T1 versus T4/T1 plot showed that, at 50% T1-block, the corresponding T4/T1 (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 (T1) tension depression, the three drugs differed widely in their ability (hexamethonium much greater than pancuronium greater than decamethonium) to produce fade as reflected in the respective train-of-four ratio. 4. Our results therefore show that the train-of-four ratio (T4/T1) at 50% T1-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 much greater than pancuronium approximately (+)-tubocurarine greater than decamethonium approximately succinylcholine much greater than alpha-bungarotoxin.