Cisatracurium besilate (INN; cisatracurium besylate (USAN); formerly recognized as 51W89;[1] trade name Nimbex) is a bisbenzyltetrahydroisoquinolinium that has effect as a neuromuscular-blocking drugnon-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. It shows intermediate duration of action. Cisatracurium is one of the ten isomers of the parent molecule, atracurium.[2] Moreover, cisatracurium represents approximately 15% of the atracurium mixture.[3]
The generic name cisatracurium was conceived by scientists at Burroughs Wellcome Co. (now part of GlaxoSmithKline) by combining the name "atracurium" with "cis" [hence cisatracurium] because the molecule is one of the three cis-cis isomers comprising the ten isomers of the parent, atracurium.[2] Atracurium itself was invented at Strathclyde University and licensed to Burroughs Wellcome Co., Research Triangle Park, NC, for further development and subsequent marketing as Tracrium. As the secondary pharmacology of atracurium was being developed, it became clear that the primary clinical disadvantage of atracurium was likely to be its propensity to elicit histamine release. To address this issue, a program was initiated to investigate the individual isomer constituents of atracurium to identify and isolate the isomer(s) associated with the undesirable histamine effects as well as identify the isomer that might possibly retain the desirable properties without the histamine release. Thus, in 1989, D A Hill and G L Turner, PhD (both chemists at Burroughs Wellcome Co., Dartford, UK) first synthesized cisatracurium as an individual isomer molecule. The pharmacological research of cisatracurium and the other individual isomers[4] was then developed further primarily by R. Brandt Maehr and William B. Wastila, PhD (both of whom were pharmacologists within the Division of Pharmacology at Burroughs Wellcome Co.) in collaboration with John J. Savarese MD (who at the time was an anesthesiologist in the Dept. of Anesthesia, Harvard Medical School at the Massachusetts General Hospital, Boston, MA). Thereafter, the entire clinical development of cisatracurium was completed in a record short period from 1992 to 1994: the team of scientists was led by J. Neal Weakly PhD, Martha M. Abou-Donia PhD, and Steve Quessy PhD, in the Division of Clinical Neurosciences at Burroughs Wellcome Co., Research Triangle Park, NC. By the time of its approval for human use, in 1995, by the US Food and Drug Administration, Burroughs Wellcome Co. had merged with Glaxo Inc., and cisatracurium was approved to be marketed as Nimbex by GlaxoWellcome Inc. The trade name "Nimbex" was derived from inserting an "i" to the original proposal "Nmbex," which stood for excellent Neuromuscular blocker.[citation needed]
Preclinical pharmacology
In vitro studies using human plasma indicated that cisatracurium spontaneously degrades at physiological pH via Hofmann elimination to yield laudanosine and the quaternary monoacrylate. Subsequent ester hydrolysis of the monoacrylate generates the monoquaternary alcohol, although the rate-limiting step is Hofmann elimination.[3] In rat plasma, cisatracurium is also metabolized by non-specific carboxylesterases (a rate-limiting step) to the monoquaternary alcohol and the monoquaternary acid.[3]
Clinical pharmacology
As is evident with the parent molecule, atracurium,[5][6] cisatracurium is also susceptible to degradation by Hofmann elimination and esterhydrolysis as components of the in vivo metabolic processes.[citation needed] See the atracurium page for information on Hofmann elimination in vivo versus the Hofmann degradation chemical reaction.
Because Hofmann elimination is a temperature- and plasma pH-dependent process, cisatracurium's rate of degradation in vivo is highly influenced by body pH and temperature just as it is with the parent molecule, atracurium: thus, an increase in body pH favors the elimination process,[citation needed] whereas a decrease in temperature slows down the process.
One of the metabolites of cisatracurium via Hofmann elimination is laudanosine – see the atracurium page for further discussion of the issue regarding this metabolite. 80% of cisatracurium is metabolized eventually to laudanosine and 20% is metabolized hepatically or excreted renally.[citation needed] 10-15% of the dose is excreted unchanged in the urine.[citation needed]
Since Hofmann elimination is an organ-independent chemodegradative mechanism, there is little or no risk to the use of cisatracurium in patients with liver or renal disease when compared with other neuromuscular-blocking agents.[7]
The two reverse ester linkages in the bridge between the two isoquinolinium groups make atracurium and cisatracurium poor targets for plasma cholinesterase, unlike mivacurium which has two conventional ester linkages.
Adverse effects
Histamine release – hypotension, reflex tachycardia and cutaneous flush
Bronchospasm – Pulmonary compliance
To date, cisatracurium has not been reported to elicit bronchospasm at doses that are clinically prescribed.
Laudanosine – Epileptic foci
Cisatracurium undergoes Hofmann elimination as a primary route of chemodegradation: consequently one of the metabolites from this process is laudanosine, a tertiary amino alkaloid reported to be a modest CNS stimulant with epileptogenic activity[8] and cardiovascular effects such as low blood pressure and a slowed heart rate.[9] As a tertiary amine, Laudanosine is unionised and readily crosses the blood–brain barrier. Presently,[when?] there is little evidence that laudanosine accumulation and related toxicity will likely ever be seen with the doses of cisatracurium that are administered in clinical practice especially given that the plasma concentrations of laudanosine generated are lower with cisatracurium than those seen with atracurium.[9]
Research
A recent[when?] study showed that cisatracurium pretreatment effectively decreases the incidence and severity of pain induced by propofol general anaesthesia. [10] Another study showed that hiccups accompanied by vomiting, insomnia, shortness of breath can also be relieved by the nondepolarizing muscle relaxant, cisatracurium, during total intravenous anesthesia.[11]
Treatment of 1,5-Pentanediol with 3-bromopropionyl chloride gives the corresponding ester; dehydrohalogenation of the ester with triethylamine then gives the bis-acrylate (2). Reaction of that unsaturated ester with tetrahydropapaverine[13][14] (3) leads to conjugate addition of the secondary amine and formation of the intermediate (4). Alkylation with methyl benzenesulfonate forms the bis-quaternary salt, affording cisatracuronium (5).
References
^Meretoja OA, Taivainen T, Wirtavuori K (Jan 1995). "Pharmacodynamic effects of 51W89, an isomer of atracurium, in children during halothane anaesthesia". Br J Anaesth. 74 (1): 6–11. doi:10.1093/bja/74.1.6. PMID 7880708.
^ abStenlake JB, Waigh RD, Dewar GH, Dhar NC, Hughes R, Chapple DJ, Lindon JC, Ferrige AG (1984). "Biodegradable neuromuscular blocking agents. Part 6. Stereochemical studies on atracurium and related polyalkylene di-esters". Eur J Med Chem. 19 (5): 441–450.
^ abcDear GJ, Harrelson JC, Jones AE, Johnson TE, Pleasance S (1995). "Identification of urinary and biliary conjugated metabolites of the neuromuscular blocker 51W89 by liquid chromatography/mass spectrometry". Rapid Commun Mass Spectrom. 9 (14): 1457–1464. Bibcode:1995RCMS....9.1457D. doi:10.1002/rcm.1290091425. PMID 8534894.
^Wastila WB, Maehr RB, Turner GL, Hill DA, Savarese JJ (Jul 1996). "Comparative pharmacology of cisatracurium (51W89), atracurium, and five isomers in cats". Anesthesiology. 85 (1): 169–177. doi:10.1097/00000542-199607000-00023. PMID 8694363. S2CID 23963554.
^Stiller RL, Cook DR, Chakravorti S (1985). "In vitro degradation of atracurium in human plasma". Br J Anaesth. 57 (11): 1085–1088. doi:10.1093/bja/57.11.1085. PMID 3840382.
^Nigrovic V, Fox JL (1991). "Atracurium decay and the formation of laudanosine in humans". Anesthesiology. 74 (3): 446–454. doi:10.1097/00000542-199103000-00010. PMID 2001023.
^Katzung, Bertram G. (2011). Basic and clinical pharmacology (12th ed.). New York: Mcgraw-Hill. ISBN978-0-07-176401-8.
^Kim YH (Apr 2014). "Cisatracurium pretreatment with tourniquet reduces propofol injection pain: a double-blind randomized controlled trial." J Int Med Res. 42 (2): 360–7. doi:10.1177/0300060514522602. PMID 24573971.
^Wu JP, An JX, Qian XY, Wang Y. Successful Treatment of Idiopathic Intractable Hiccup With Cisatracurium Under Intravenous General Anesthesia: A Case Report. A A Pract. 2018;10(7):171‐172. doi:10.1213/XAA.0000000000000651
^D. A. Hill, G. L. Turner U.S. Patent 5,453,510 (1995).
^Schmidt, Andreas (2003). "Heterocyclic Mesomeric Betaines and Analogs in Natural Product Chemistry. Betainic Alkaloids and Nucleobases". Advances in Heterocyclic Chemistry Volume 85. Advances in Heterocyclic Chemistry. Vol. 85. pp. 67–171. doi:10.1016/S0065-2725(03)85002-X. ISBN978-0-12-020785-5.
^Chandra, Ramesh; Kaur, Jaskiran; Talwar, Anita; Ghosh, Narendra N. (2001). "Synthesis and antispasmodic effect of aryl substituted N-carbamoyl/thiocarbamoyl isoquinolines". Arkivoc. 2001 (8): 129–135. doi:10.3998/ark.5550190.0002.814.
Further reading
Caldwell JE (1995). "New skeletal muscle relaxants". Int Anesthesiol Clin. 33 (1): 39–60. doi:10.1097/00004311-199500000-00003. PMID 7635557.
Hull CJ (1995). "Pharmacokinetics and pharmacodynamics of the benzylisoquinolinium muscle relaxants". Acta Anaesthesiol Scand. 106 Suppl: 13–17. doi:10.1111/j.1399-6576.1995.tb04302.x. PMID 8533537. S2CID 43784865.
Savarese JJ, Wastila WB (1995). "The future of the benzylisoquinolinium relaxants". Acta Anaesthesiol Scand. 106 Suppl: 91–93. doi:10.1111/j.1399-6576.1995.tb04317.x. PMID 8533554. S2CID 39461057.
Esmaoglu A, Akin A, Mizrak A, Turk Y, Boyaci A (2006). "Addition of cisatracurium to lidocaine for intravenous regional anesthesia". J Clin Anesth. 18 (3): 194–7. doi:10.1016/j.jclinane.2005.08.003. PMID 16731321.
Melloni C, De Vivo P, Launo C, Mastronardi P, Novelli G, Romano E (2006). "Cisatracurium versus vecuronium: a comparative, double blind, randomized, multicenter study in adult patients under propofol/fentanyl/N2O anesthesia". Minerva Anestesiol. 72 (5): 299–308. PMID 16675938.
Serra C, Oliveira A (2006). "Cisatracurium: myographical and electrophysiological studies in the isolated rat muscle". Fundam Clin Pharmacol. 20 (3): 291–8. doi:10.1111/j.1472-8206.2006.00395.x. PMID 16671964. S2CID 11980810.
Katzung, Bertram G. (2011). Basic and clinical pharmacology (12th ed.). New York: Mcgraw-Hill. ISBN978-0-07-176401-8.
External links
"Cisatracurium besylate". Drug Information Portal. U.S. National Library of Medicine.
"Cisatracurium". Drug Information Portal. U.S. National Library of Medicine.
cisatracurium, besilate, cisatracurium, besylate, usan, formerly, recognized, 51w89, trade, name, nimbex, bisbenzyltetrahydroisoquinolinium, that, effect, neuromuscular, blocking, drug, depolarizing, neuromuscular, blocking, drugs, used, adjunctively, anesthes. Cisatracurium besilate INN cisatracurium besylate USAN formerly recognized as 51W89 1 trade name Nimbex is a bisbenzyltetrahydroisoquinolinium that has effect as a neuromuscular blocking drug non depolarizing neuromuscular blocking drugs used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation It shows intermediate duration of action Cisatracurium is one of the ten isomers of the parent molecule atracurium 2 Moreover cisatracurium represents approximately 15 of the atracurium mixture 3 Cisatracurium besilateClinical dataTrade namesNimbexOther names51W89 cisatracurium besylate USAN US AHFS Drugs comMonographLicense dataUS DailyMed Cisatracurium besylatePregnancycategoryAU CRoutes ofadministrationIntravenousATC codeM03AC11 WHO Legal statusLegal statusAU S4 Prescription only CA only UK POM Prescription only US only In general Prescription only Pharmacokinetic dataBioavailability100 IV Metabolism80 Hofmann degradation liverElimination half life20 29 minutesExcretion10 15 unchangedIdentifiersIUPAC name 5 3 1R 2R 1 3 4 Dimethoxyphenyl methyl 6 7 dimethoxy 2 methyl 3 4 dihydro 1H isoquinolin 2 yl propanoyloxy pentyl 3 1R 2R 1 3 4 dimethoxyphenyl methyl 6 7 dimethoxy 2 methyl 3 4 dihydro 1H isoquinolin 2 yl propanoate benzenesulfonate 1 2 CAS Number96946 42 8 Y96946 41 7PubChem CID6288662887DrugBankDBSALT002671 YDB00565ChemSpider56614 Y56615UNII80YS8O1MBSQX62KLI41NKEGGD00759ChEBICHEBI 3721 YCHEBI 140621ChEMBLChEMBL1200641 NChEMBL1201248CompTox Dashboard EPA DTXSID10895045ECHA InfoCard100 149 509Chemical and physical dataFormulaC 65H 82N 2O 18S 2Molar mass1243 49 g mol 13D model JSmol Interactive imageSMILES O S O O c1ccccc1 O S O O c1ccccc1 O C OCCCCCOC O CC N 2 C H c1c cc OC c OC c1 CC2 Cc3ccc OC c OC c3 C CC N 5 C C H c4cc OC c OC cc4CC5 Cc6ccc OC c OC c6InChI InChI 1S C53H72N2O12 2C6H6O3S c1 54 22 18 38 32 48 62 7 50 64 9 34 40 38 42 54 28 36 14 16 44 58 3 46 30 36 60 5 24 20 52 56 66 26 12 11 13 27 67 53 57 21 25 55 2 23 19 39 33 49 63 8 51 65 10 35 41 39 43 55 29 37 15 17 45 59 4 47 31 37 61 6 2 7 10 8 9 6 4 2 1 3 5 6 h14 17 30 35 42 43H 11 13 18 29H2 1 10H3 2 1 5H H 7 8 9 q 2 p 2 t42 43 54 55 m1 s1 YKey XXZSQOVSEBAPGS DONVQRBFSA L Y N Y what is this verify Contents 1 History 2 Preclinical pharmacology 3 Clinical pharmacology 4 Adverse effects 4 1 Histamine release hypotension reflex tachycardia and cutaneous flush 4 2 Bronchospasm Pulmonary compliance 4 3 Laudanosine Epileptic foci 5 Research 6 Synthesis 7 References 8 Further reading 9 External linksHistory EditThe generic name cisatracurium was conceived by scientists at Burroughs Wellcome Co now part of GlaxoSmithKline by combining the name atracurium with cis hence cisatracurium because the molecule is one of the three cis cis isomers comprising the ten isomers of the parent atracurium 2 Atracurium itself was invented at Strathclyde University and licensed to Burroughs Wellcome Co Research Triangle Park NC for further development and subsequent marketing as Tracrium As the secondary pharmacology of atracurium was being developed it became clear that the primary clinical disadvantage of atracurium was likely to be its propensity to elicit histamine release To address this issue a program was initiated to investigate the individual isomer constituents of atracurium to identify and isolate the isomer s associated with the undesirable histamine effects as well as identify the isomer that might possibly retain the desirable properties without the histamine release Thus in 1989 D A Hill and G L Turner PhD both chemists at Burroughs Wellcome Co Dartford UK first synthesized cisatracurium as an individual isomer molecule The pharmacological research of cisatracurium and the other individual isomers 4 was then developed further primarily by R Brandt Maehr and William B Wastila PhD both of whom were pharmacologists within the Division of Pharmacology at Burroughs Wellcome Co in collaboration with John J Savarese MD who at the time was an anesthesiologist in the Dept of Anesthesia Harvard Medical School at the Massachusetts General Hospital Boston MA Thereafter the entire clinical development of cisatracurium was completed in a record short period from 1992 to 1994 the team of scientists was led by J Neal Weakly PhD Martha M Abou Donia PhD and Steve Quessy PhD in the Division of Clinical Neurosciences at Burroughs Wellcome Co Research Triangle Park NC By the time of its approval for human use in 1995 by the US Food and Drug Administration Burroughs Wellcome Co had merged with Glaxo Inc and cisatracurium was approved to be marketed as Nimbex by GlaxoWellcome Inc The trade name Nimbex was derived from inserting an i to the original proposal Nmbex which stood for excellent Neuromuscular blocker citation needed Preclinical pharmacology EditIn vitro studies using human plasma indicated that cisatracurium spontaneously degrades at physiological pH via Hofmann elimination to yield laudanosine and the quaternary monoacrylate Subsequent ester hydrolysis of the monoacrylate generates the monoquaternary alcohol although the rate limiting step is Hofmann elimination 3 In rat plasma cisatracurium is also metabolized by non specific carboxylesterases a rate limiting step to the monoquaternary alcohol and the monoquaternary acid 3 Clinical pharmacology EditAs is evident with the parent molecule atracurium 5 6 cisatracurium is also susceptible to degradation by Hofmann elimination and ester hydrolysis as components of the in vivo metabolic processes citation needed See the atracurium page for information on Hofmann elimination in vivo versus the Hofmann degradation chemical reaction Because Hofmann elimination is a temperature and plasma pH dependent process cisatracurium s rate of degradation in vivo is highly influenced by body pH and temperature just as it is with the parent molecule atracurium thus an increase in body pH favors the elimination process citation needed whereas a decrease in temperature slows down the process One of the metabolites of cisatracurium via Hofmann elimination is laudanosine see the atracurium page for further discussion of the issue regarding this metabolite 80 of cisatracurium is metabolized eventually to laudanosine and 20 is metabolized hepatically or excreted renally citation needed 10 15 of the dose is excreted unchanged in the urine citation needed Since Hofmann elimination is an organ independent chemodegradative mechanism there is little or no risk to the use of cisatracurium in patients with liver or renal disease when compared with other neuromuscular blocking agents 7 The two reverse ester linkages in the bridge between the two isoquinolinium groups make atracurium and cisatracurium poor targets for plasma cholinesterase unlike mivacurium which has two conventional ester linkages Adverse effects EditHistamine release hypotension reflex tachycardia and cutaneous flush Edit Bronchospasm Pulmonary compliance Edit To date cisatracurium has not been reported to elicit bronchospasm at doses that are clinically prescribed Laudanosine Epileptic foci Edit Cisatracurium undergoes Hofmann elimination as a primary route of chemodegradation consequently one of the metabolites from this process is laudanosine a tertiary amino alkaloid reported to be a modest CNS stimulant with epileptogenic activity 8 and cardiovascular effects such as low blood pressure and a slowed heart rate 9 As a tertiary amine Laudanosine is unionised and readily crosses the blood brain barrier Presently when there is little evidence that laudanosine accumulation and related toxicity will likely ever be seen with the doses of cisatracurium that are administered in clinical practice especially given that the plasma concentrations of laudanosine generated are lower with cisatracurium than those seen with atracurium 9 Research EditA recent when study showed that cisatracurium pretreatment effectively decreases the incidence and severity of pain induced by propofol general anaesthesia 10 Another study showed that hiccups accompanied by vomiting insomnia shortness of breath can also be relieved by the nondepolarizing muscle relaxant cisatracurium during total intravenous anesthesia 11 Synthesis Edit Cisatracuronium synthesis 12 Treatment of 1 5 Pentanediol with 3 bromopropionyl chloride gives the corresponding ester dehydrohalogenation of the ester with triethylamine then gives the bis acrylate 2 Reaction of that unsaturated ester with tetrahydropapaverine 13 14 3 leads to conjugate addition of the secondary amine and formation of the intermediate 4 Alkylation with methyl benzenesulfonate forms the bis quaternary salt affording cisatracuronium 5 References Edit Meretoja OA Taivainen T Wirtavuori K Jan 1995 Pharmacodynamic effects of 51W89 an isomer of atracurium in children during halothane anaesthesia Br J Anaesth 74 1 6 11 doi 10 1093 bja 74 1 6 PMID 7880708 a b Stenlake JB Waigh RD Dewar GH Dhar NC Hughes R Chapple DJ Lindon JC Ferrige AG 1984 Biodegradable neuromuscular blocking agents Part 6 Stereochemical studies on atracurium and related polyalkylene di esters Eur J Med Chem 19 5 441 450 a b c Dear GJ Harrelson JC Jones AE Johnson TE Pleasance S 1995 Identification of urinary and biliary conjugated metabolites of the neuromuscular blocker 51W89 by liquid chromatography mass spectrometry Rapid Commun Mass Spectrom 9 14 1457 1464 Bibcode 1995RCMS 9 1457D doi 10 1002 rcm 1290091425 PMID 8534894 Wastila WB Maehr RB Turner GL Hill DA Savarese JJ Jul 1996 Comparative pharmacology of cisatracurium 51W89 atracurium and five isomers in cats Anesthesiology 85 1 169 177 doi 10 1097 00000542 199607000 00023 PMID 8694363 S2CID 23963554 Stiller RL Cook DR Chakravorti S 1985 In vitro degradation of atracurium in human plasma Br J Anaesth 57 11 1085 1088 doi 10 1093 bja 57 11 1085 PMID 3840382 Nigrovic V Fox JL 1991 Atracurium decay and the formation of laudanosine in humans Anesthesiology 74 3 446 454 doi 10 1097 00000542 199103000 00010 PMID 2001023 Katzung Bertram G 2011 Basic and clinical pharmacology 12th ed New York Mcgraw Hill ISBN 978 0 07 176401 8 Standaert FG Dec 1985 Magic bullets science and medicine Anesthesiology 63 6 577 578 doi 10 1097 00000542 198512000 00002 PMID 2932980 a b Fodale V Santamaria LB Jul 2002 Laudanosine an atracurium and cisatracurium metabolite Eur J Anaesthesiol 19 7 466 473 doi 10 1017 s0265021502000777 PMID 12113608 Kim YH Apr 2014 Cisatracurium pretreatment with tourniquet reduces propofol injection pain a double blind randomized controlled trial J Int Med Res 42 2 360 7 doi 10 1177 0300060514522602 PMID 24573971 Wu JP An JX Qian XY Wang Y Successful Treatment of Idiopathic Intractable Hiccup With Cisatracurium Under Intravenous General Anesthesia A Case Report A A Pract 2018 10 7 171 172 doi 10 1213 XAA 0000000000000651 D A Hill G L Turner U S Patent 5 453 510 1995 Schmidt Andreas 2003 Heterocyclic Mesomeric Betaines and Analogs in Natural Product Chemistry Betainic Alkaloids and Nucleobases Advances in Heterocyclic Chemistry Volume 85 Advances in Heterocyclic Chemistry Vol 85 pp 67 171 doi 10 1016 S0065 2725 03 85002 X ISBN 978 0 12 020785 5 Chandra Ramesh Kaur Jaskiran Talwar Anita Ghosh Narendra N 2001 Synthesis and antispasmodic effect of aryl substituted N carbamoyl thiocarbamoyl isoquinolines Arkivoc 2001 8 129 135 doi 10 3998 ark 5550190 0002 814 Further reading EditCaldwell JE 1995 New skeletal muscle relaxants Int Anesthesiol Clin 33 1 39 60 doi 10 1097 00004311 199500000 00003 PMID 7635557 Hull CJ 1995 Pharmacokinetics and pharmacodynamics of the benzylisoquinolinium muscle relaxants Acta Anaesthesiol Scand 106 Suppl 13 17 doi 10 1111 j 1399 6576 1995 tb04302 x PMID 8533537 S2CID 43784865 Savarese JJ Wastila WB 1995 The future of the benzylisoquinolinium relaxants Acta Anaesthesiol Scand 106 Suppl 91 93 doi 10 1111 j 1399 6576 1995 tb04317 x PMID 8533554 S2CID 39461057 Esmaoglu A Akin A Mizrak A Turk Y Boyaci A 2006 Addition of cisatracurium to lidocaine for intravenous regional anesthesia J Clin Anesth 18 3 194 7 doi 10 1016 j jclinane 2005 08 003 PMID 16731321 Melloni C De Vivo P Launo C Mastronardi P Novelli G Romano E 2006 Cisatracurium versus vecuronium a comparative double blind randomized multicenter study in adult patients under propofol fentanyl N2O anesthesia Minerva Anestesiol 72 5 299 308 PMID 16675938 Serra C Oliveira A 2006 Cisatracurium myographical and electrophysiological studies in the isolated rat muscle Fundam Clin Pharmacol 20 3 291 8 doi 10 1111 j 1472 8206 2006 00395 x PMID 16671964 S2CID 11980810 Katzung Bertram G 2011 Basic and clinical pharmacology 12th ed New York Mcgraw Hill ISBN 978 0 07 176401 8 External links Edit Cisatracurium besylate Drug Information Portal U S National Library of Medicine Cisatracurium Drug Information Portal U S National Library of Medicine Portal Medicine Retrieved from https en wikipedia org w index php title Cisatracurium besilate amp oldid 1136105851, wikipedia, wiki, book, books, library,
