H Fajrak, Ian. G Marshall, C Prior,
Volume 13, Issue 2 (8-1999)
Abstract
The potential changes In neuromuscular blockade after chronic (>24 h)
administration of sub-paralytic doses of two newly introduced aminosteroidal
muscle relaxants were investigated. Org-9426 (rocuronium) and Org-9487 were
studied in the in vivo guinea pig gastrocnemius muscle-sciatic nerve preparation.
The problems seen after prolonged administration of muscle relaxants are thought
to arise from up-regulation of AChRs and this phenomenon may be responsible,
at least in part, for prolonged muscle paralysis, development of resistance to
muscle relaxants and generalized muscle weakness seen with chronic administration.
After two weeks of chronic treatment, using implanted osmotic mini-pumps
delivering sub-paralytic doses of the test drugs, responsiveness to the muscle
relaxants altered significantly so that higher doses were required in the drug pretreated
groups to produce the same twitch block as in matched control animals. A
possible explanation for this observation is that, following chronic treatment, upregulation
of AChRs occurs, at the neuromuscular junction, thus increasing the
required doses in the drug pre-treated animals as compared with the control group.
