%0 Journal Article %A FAJRAK, H %A MARSHALL, IAN. G %A PRIOR, C %T EFFECTS OF CHRONIC ADMINISTRATION OF TWO NEWLY SYNTHESIZED NONDEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS %J Medical Journal of the Islamic Republic Of Iran %V 13 %N 2 %U http://mjiri.iums.ac.ir/article-1-959-en.html %R %D 1999 %K Up-regulation, Neuromuscular junction, Chronic administration, Org-9487, Org- 9426., %X 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. %> http://mjiri.iums.ac.ir/article-1-959-en.pdf %P 143-149 %& 143 %! Chronic Neuromuscular Blockade %9 Original Research: Basic Science in Medicine %L A-10-298-410 %+ From the Dept. of Pharmacology and Toxicology, Baghyatallah University of Medical Sciences, Tehran, I.R. Iran %G eng %@ 1016-1430 %[ 1999