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 ResearchMeSH KeywordsAnimalsBlood PressureCysteineHeart RateHumansMacaca mulattaMaleModels, AnimalNeuromuscular BlockadeNeuromuscular Blocking AgentsConceptsNeuromuscular 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 concentrationCW002
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 ResearchMeSH KeywordsCysteineGamma-CyclodextrinsHumansIsoquinolinesNeuromuscular BlockadeNeuromuscular Nondepolarizing AgentsSugammadexConceptsMuscle relaxantsClinical trialsNeuromuscular blocking drugsNondepolarizing muscle relaxantsNew muscle relaxantsL-cysteine injectionNondepolarizing drugSugammadex reversalBlocking drugsHistamine releasePreclinical studiesComplete paralysisCysteine injectionClinical developmentCW002RelaxantsRapid reversalIntermediate durationDrugsGantacuriumTrialsInjectionDurationRocuroniumSugammadexEffect of gantacurium on evoked laryngospasm and duration of apnea in anesthetized healthy cats.
Martin-Flores M, Cheetham J, Campoy L, Sakai DM, Heerdt PM, Gleed RD. Effect of gantacurium on evoked laryngospasm and duration of apnea in anesthetized healthy cats. American Journal Of Veterinary Research 2015, 76: 216-23. PMID: 25710757, DOI: 10.2460/ajvr.76.3.216.Peer-Reviewed Original ResearchConceptsDuration of apneaHemoglobin oxygen saturationLast doseLaryngeal stimulationNeuromuscular blockOxygen saturationPelvic limbsLaryngeal mask airwayComplete neuromuscular blockDomestic shorthair catAdult domestic shorthair catsHealthy adult domestic shorthair catsMask airwayLaryngeal maskSE durationAnesthetized catsHemoglobin desaturationLaryngospasmShorthair catClinical relevanceGantacuriumHealthy catsApneaRima glottidisDose
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 chromatographyBlockers