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
2015
Novel neuromuscular blocking drugs and antagonists
Heerdt PM, Sunaga H, Savarese JJ. Novel neuromuscular blocking drugs and antagonists. Current Opinion In Anaesthesiology 2015, 28: 403-410. PMID: 26087274, DOI: 10.1097/aco.0000000000000209.Peer-Reviewed Original ResearchConceptsMuscle relaxantsClinical trialsNeuromuscular blocking drugsNondepolarizing muscle relaxantsNew muscle relaxantsL-cysteine injectionNondepolarizing drugSugammadex reversalBlocking drugsHistamine releasePreclinical studiesComplete paralysisCysteine injectionClinical developmentCW002RelaxantsRapid reversalIntermediate durationDrugsGantacuriumTrialsInjectionDurationRocuroniumSugammadex
2014
Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits.
Diaz LL, Zhang J, Heerdt PM. Comparative pharmacodynamics of pancuronium, cisatracurium, and CW002 in rabbits. Journal Of The American Association For Laboratory Animal Science 2014, 53: 283-9. PMID: 24827571, PMCID: PMC4128567.Peer-Reviewed Original ResearchConceptsNeuromuscular blocking drugsRecovery indexNew Zealand white rabbitsPotential side effectsCross-over designZealand white rabbitsComparative PharmacodynamicsBlocking drugsPharmacologic reversalMuscle twitchCisatracuriumPancuroniumAnesthetized rabbitsSide effectsCW002Cholinergic manipulationsSurvival proceduresSimilar onsetWhite rabbitsEffective doseSurvival studiesLonger durationDrugsRabbitsTime course
2010
Pharmacodynamics 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 dosesCW002Cysteine 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 groupDose