In vitro time course studies on train-of-four fade induced by hexamethonium, pancuronium and decamethonium in the rat hemidiaphragm.
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.
Gwee
M C
MC
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
Cheah
L S
LS
D000818:Animals; D003650:Decamethonium Compounds / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D005260:Female; D006584:Hexamethonium Compounds / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010197:Pancuronium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012132:Respiratory Muscles / Q000187:drug effects* / Q000502:physiology
D003650:Decamethonium Compounds; D006584:Hexamethonium Compounds; D010197:Pancuronium