Examination of the mechanisms involved in tetanic fade produced by vecuronium and related analogues in the rat diaphragm.
The effects of vecuronium (Org NC45), Org 7678 and Org 7684 were examined on twitches and tetani recorded from rat isolated diaphragms. Org 7678 and Org 7684 exhibited approximately one tenth of the neuromuscular blocking potency of vecuronium. At concentrations producing equivalent amounts of twitch block, Org 7684 produced significantly less tetanic fade than did vecuronium or Org 7678. In cut muscles both vecuronium and Org 7684 reduced the endplate current (e.p.c.) amplitude (Ie.p.c.), reduced e.p.c. decay time constant (tau e.p.c.), and increased the e.p.c. train rundown. The effects of vecuronium were not voltage-dependent and vecuronium did not change tau noise. The effect of Org 7684 on Ie.p.c. and tau e.p.c. became greater with hyperpolarization, but the effect on e.p.c. train rundown was not voltage-dependent. It is concluded that both vecuronium and Org 7684 produce e.p.c. train rundown and tetanic fade by a prejunctional mechanism. However, whereas postjunctionally vecuronium blocks only the acetylcholine receptor, Org 7684 blocks both the receptor and its associated ion channel.
D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012132:Respiratory Muscles / Q000187:drug effects*; D014673:Vecuronium Bromide / Q000031:analogs & derivatives* / Q000494:pharmacology*
C052040:Org 7678; C052039:Org 7684; D014673:Vecuronium Bromide