| Pharmacodynamics and cardiopulmonary side effects of CW002, a cysteine-reversible neuromuscular blocking drug in dogs. | |
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MedLine Citation:
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PMID: 20234311 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: CW002 is a novel neuromuscular blocking drug with a duration dependent on the rate of cysteine adduction to the molecule. The current study characterized the pharmacodynamics and cardiopulmonary side effects of CW002 in dogs. METHODS: In eight beagles, the dose required to produce 95% neuromuscular blockade (ED95) for CW002 was first determined and cysteine reversibility was confirmed. Five to 7 days later, incrementally larger doses were injected starting with 6.25 x ED95 and doubling the dose every 15 min. Before and after injection, blood was obtained for histamine analysis. Systemic and pulmonary arterial pressures, cardiac output, and left ventricular pressure and volume were recorded along with inspiratory pressure and pulmonary compliance. Ventricular contractility and lusitropy were indexed from pressure and volume data. RESULTS: The ED95 for CW002 from pooled data was 0.009 mg/kg. At 3 x ED95, onset time was 2.6 +/- 0.9 min and duration was 47 +/- 9 min. The duration was shortened to 3.7 +/- 0.6 min by 50 mg/kg L-cysteine injected 1 min after CW002. At 25 x ED95, CW002 reduced mean arterial pressure with concomitant decreases in systemic vascular resistance, mean pulmonary artery pressure, cardiac output, contractility, and lusitropy, beginning at 50 x ED95. However, even at a dose of 100 x ED95, the average change in any variable was less than 20%. There were no changes in pulmonary vascular resistance or ventilation mechanics at any dose, and histamine release occurred in only two of eight animals. CONCLUSIONS: CW002 is a potent neuromuscular blocking drug that at doses up to 100 x ED95 produces modest hemodynamic effects that are not associated with bronchoconstriction or consistent histamine release. |
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Authors:
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Paul M Heerdt; Jaideep K Malhotra; Brian Y Pan; Hiroshi Sunaga; John J Savarese |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anesthesiology Volume: 112 ISSN: 1528-1175 ISO Abbreviation: Anesthesiology Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-14 Completed Date: 2010-05-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
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Languages: eng Pagination: 910-6 Citation Subset: AIM; IM |
Affiliation:
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Departments of Anesthesiology of Pharmacology, Weill Medical College of Cornell University, New York, New York, USA. pmheerd@mail.med.cornell.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects Cysteine / pharmacology* Data Interpretation, Statistical Dogs Dose-Response Relationship, Drug Heart Rate / drug effects Hemodynamics / drug effects* Histamine Release / drug effects Isoquinolines / antagonists & inhibitors*, pharmacology*, toxicity Lung / drug effects* Lung Compliance / drug effects Neuromuscular Blocking Agents / antagonists & inhibitors*, pharmacology*, toxicity Respiratory Function Tests Respiratory Mechanics / drug effects |
| Chemical | |
Reg. No./Substance:
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0/CW 002; 0/Isoquinolines; 0/Neuromuscular Blocking Agents; 52-90-4/Cysteine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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