2018
Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine.
Savarese JJ, Sunaga H, McGilvra JD, Belmont MR, Murrell MT, Jeannotte E, Cooke FE, Wastila WB, Heerdt PM. Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine. Anesthesiology 2018, 129: 970-988. PMID: 30212413, DOI: 10.1097/aln.0000000000002408.Peer-Reviewed Original ResearchConceptsNeuromuscular blocking agentsMean arterial pressureBlocking agentArterial pressureNeuromuscular blockadeHeart rateNew neuromuscular blocking agentRhesus monkeysNondepolarizing neuromuscular blocking agentDuration of actionStudy of bolusCirculatory effectsPreclinical pharmacologyControl infusionInstitutional Animal CareED95Large dosesSpontaneous recoveryGantacuriumDose ratioL-cysteineInfusionBolusUse CommitteeRecovery interval
2016
Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man
Heerdt PM, Sunaga H, Owen JS, Murrell MT, Malhotra JK, Godfrey D, Steinkamp M, Savard P, Savarese JJ, Lien CA. Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man. Anesthesiology 2016, 125: 1136-1143. PMID: 27749289, DOI: 10.1097/aln.0000000000001386.Peer-Reviewed Original ResearchConceptsCardiopulmonary side effectsHistamine releaseSide effectsBlood pressureHealthy subjectsHeart rateSevoflurane/nitrous oxideDose-escalation clinical trialDynamic airway complianceNeuromuscular-blocking drugsEscalation clinical trialPlasma histamine concentrationSigmoid Emax modelClinical recoveryClinical durationAdductor pollicisTwitch depressionAirway complianceNeuromuscular blockadeClinical trialsPreclinical studiesArterial bloodEmax modelHistamine concentrationCW002Preclinical Pharmacology of CW002
Sunaga H, Savarese JJ, McGilvra JD, Heerdt PM, Belmont MR, Van Ornum SG, Murrell MT, Malhotra JK, Savard PM, Jeannotte E, Petty BJ, Allen E, Carnathan GW. Preclinical Pharmacology of CW002. Anesthesiology 2016, 125: 732-743. PMID: 27466033, DOI: 10.1097/aln.0000000000001254.Peer-Reviewed Original ResearchMean arterial pressureNeuromuscular blockadeArterial pressureNondepolarizing neuromuscular blocking agentDose ratioSympathetic autonomic responsesNeuromuscular blocking agentsNeuromuscular blocking propertiesRecovery intervalIncrease of HRSympathetic inhibitionBolus dosesCirculatory effectsPreclinical pharmacologyTwitch inhibitionBlocking agentStudy of safetyInstitutional Animal CareAnesthetized monkeysHeart rateSpontaneous recoveryED95CW002Autonomic responsesRapid reversal
2010
Rapid Chemical Antagonism of Neuromuscular Blockade by l-Cysteine Adduction to and Inactivation of the Olefinic (Double-bonded) Isoquinolinium Diester Compounds Gantacurium (AV430A), CW 002, and CW 011
Savarese JJ, McGilvra JD, Sunaga H, Belmont MR, Van Ornum SG, Savard PM, Heerdt PM. Rapid Chemical Antagonism of Neuromuscular Blockade by l-Cysteine Adduction to and Inactivation of the Olefinic (Double-bonded) Isoquinolinium Diester Compounds Gantacurium (AV430A), CW 002, and CW 011. Anesthesiology 2010, 113: 58-73. PMID: 20526187, DOI: 10.1097/aln.0b013e3181dc1b5b.Peer-Reviewed Original ResearchMeSH KeywordsAlkenesAnimalsAtracuriumChemical PhenomenaCholinesterase InhibitorsChromatography, High Pressure LiquidCysteineDose-Response Relationship, DrugDrug InteractionsEdrophoniumHaplorhiniIsoquinolinesMacaca mulattaMaleMaleatesNeostigmineNeuromuscular BlockadeNeuromuscular Blocking AgentsStructure-Activity RelationshipConceptsDuration of blockED95 dosesNeuromuscular blockadeNeuromuscular blockersNovel agentsTwitch inhibitionCysteine adductionGantacuriumExogenous L-cysteineIntermediate durationAdductionL-cysteineED95Preliminary dataBlockadeAntagonismChemical antagonismHigh-performance liquid chromatographyDurationMinRapid adductionAdduction productsCisatracuriumLiquid chromatographyBlockersCysteine Reversal of the Novel Neuromuscular Blocking Drug CW002 in Dogs
Sunaga H, Malhotra JK, Yoon E, Savarese JJ, Heerdt PM. Cysteine Reversal of the Novel Neuromuscular Blocking Drug CW002 in Dogs. Anesthesiology 2010, 112: 900-909. PMID: 20234310, DOI: 10.1097/aln.0b013e3181d31f8c.Peer-Reviewed Original ResearchConceptsOrgan toxicityHeart rateIsoflurane-nitrous oxide anesthesiaAcute cardiovascular effectsNeuromuscular blocking drugsDose-response relationshipDose-dependent mannerEndogenous L-cysteineCardiovascular effectsHemodynamic effectsMedian durationArterial pressureBlood pressureBlocking drugsHistologic evidenceNeuromuscular blockadeOxide anesthesiaTwitch recoveryMuscle recoveryHistopathologic analysisMuscle twitchLarge doseCW002Additional groupDosePharmacodynamics and Cardiopulmonary Side Effects of CW002, a Cysteine-reversible Neuromuscular Blocking Drug in Dogs
Heerdt PM, Malhotra JK, Pan BY, Sunaga H, Savarese JJ. Pharmacodynamics and Cardiopulmonary Side Effects of CW002, a Cysteine-reversible Neuromuscular Blocking Drug in Dogs. Anesthesiology 2010, 112: 910-916. PMID: 20234311, DOI: 10.1097/aln.0b013e3181d31f71.Peer-Reviewed Original ResearchConceptsX ED95Neuromuscular blocking drugsCardiopulmonary side effectsVascular resistanceArterial pressureBlocking drugsCardiac outputHistamine releaseSide effectsMean pulmonary artery pressurePulmonary artery pressurePulmonary vascular resistanceSystemic vascular resistanceMean arterial pressurePulmonary arterial pressureArtery pressureHemodynamic effectsPulmonary complianceVentricular contractilityInspiratory pressureNeuromuscular blockadeVentricular pressureED95Large dosesCW002
2004
Cardiopulmonary Effects of the Novel Neuromuscular Blocking Drug GW280430A (AV430A) in Dogs
Heerdt PM, Kang R, The’ A, Hashim M, Mook RJ, Savarese JJ. Cardiopulmonary Effects of the Novel Neuromuscular Blocking Drug GW280430A (AV430A) in Dogs. Anesthesiology 2004, 100: 846-851. PMID: 15087619, DOI: 10.1097/00000542-200404000-00014.Peer-Reviewed Original ResearchConceptsX ED95Cardiopulmonary changesBolus dosingDirect myocardial depressionStable neuromuscular blockadeMean arterial pressurePlasma histamine concentrationCardiopulmonary side effectsNondepolarizing neuromuscularPulmonary vasoconstrictionArterial pressureCardiovascular effectsMyocardial depressionCardiopulmonary effectsHemodynamic measurementsInspiratory pressureNeuromuscular blockadePulmonary complianceAnesthetized dogsCardiopulmonary dataMale beaglesArterial bloodED95Heart rateSide effects