title: Conscious and anesthetized non-human primate safety pharmacology models: hemodynamic sensitivity comparison.
abstract: BACKGROUND
  Drug-induced cardiovascular effects identified in conscious cynomolgus monkeys equipped with tethers and prepared for radiotelemetry were compared with results from anesthetized non-human primate (cynomolgus and rhesus) models.
  
  
  METHODS
  Remifentanil (4.0 microg/kg, bolus), esmolol (2.0 mg/kg, bolus) and dopamine (0.05 mg/kg/min, 30 min infusion) were given intravenously to all models.
  
  
  RESULTS
  Remifentanil decreased heart rate (HR), systolic, mean and diastolic systemic arterial pressures (SAP) in anesthetized animals while conscious monkeys presented an increase in HR, systolic, mean and diastolic SAP, as seen in humans for the respective state of consciousness (conscious and anesthetized). Esmolol decreased HR, systolic, mean and diastolic SAP in anesthetized monkeys while only HR, systolic and mean SAP achieved a statistically significant decrease in the conscious model. The amplitude of SAP reduction was greater in anesthetized models, while the amplitude of HR reduction was greater in the conscious and anesthetized cynomolgus models than in the anesthetized rhesus model. Dopamine induced a significant increase in HR, systolic, mean and diastolic SAP in anesthetized models without any statistically significant effect on HR and SAP in the conscious model.
  
  
  CONCLUSIONS
  The amplitude of hemodynamic and chronotropic alterations induced by positive control drugs was generally greater in anesthetized than in conscious models and statistical significance was achieved more often with the anesthetized models. These results suggest that an anesthetized model may be valuable as part of a drug screening program for cardiovascular safety evaluations in addition to a conscious model.
authors.affiliation: LAB Research Inc, 445 Armand Frappier, Laval, Quebec, Canada. authiers@labresearch.com
authors.forename: S
authors.initials: S
authors.lastname: Authier
authors.forename: J F
authors.initials: JF
authors.lastname: Tanguay
authors.forename: S
authors.initials: S
authors.lastname: Fournier
authors.forename: D
authors.initials: D
authors.lastname: Gauvin
authors.forename: M
authors.initials: M
authors.lastname: Legaspi
authors.forename: F
authors.initials: F
authors.lastname: Chaurand
authors.forename: C
authors.initials: C
authors.lastname: Breault
authors.forename: E
authors.initials: E
authors.lastname: Troncy
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects; D000758:Anesthesia; D000818:Animals; D003243:Consciousness; D004298:Dopamine / Q000009:adverse effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006993:Hypnotics and Sedatives / Q000009:adverse effects; D008252:Macaca fascicularis; D008297:Male; D010880:Piperidines / Q000009:adverse effects*; D011412:Propanolamines / Q000009:adverse effects*; D000077208:Remifentanil; D013566:Sympathomimetics / Q000009:adverse effects; D013686:Telemetry
chemical_list: D000319:Adrenergic beta-Antagonists; D006993:Hypnotics and Sedatives; D010880:Piperidines; D011412:Propanolamines; D013566:Sympathomimetics; C036604:esmolol; D000077208:Remifentanil; D004298:Dopamine