Conscious Dogs General Pharmacology Evaluation Of QO-58lysine

Safety pharmacology is the study of the potential undesirable pharmacodynamics effects of a drug in relation to dosage within the drug's therapeutic range and above.In particular,the study targeting mainly unintended effects should be investigated,e.g.nerve system,cardiovascular system and respiratory system and have been an important contents for preclinical evaluation of a new drug.Implantable telemetry system by the means of implanting wireless sensors in animal body and taking advantage of electronic receivers can continuously monitor physiological parameters in vivo.This thesis has finished the 3Q qualification for the implantable telemetry system manufactured by DSI company,and observed the effect of QO-58 lysine on the cardiovascular,respiratory system,for exploring the new chemical compoundfurther.Part1 establishment and qualification of the implantable telemetry systemObjective: To establish the implantable telemetry system and get the 3 kinds of qualification.Methods:The sensors are planted into the beagle dogs' body by surgical operation and then record and analysis the physiological parameters under free circumstance.Under collection of this apparatus dataas a background information for 24 hours,a chemical drug called terfenadine as a positive compound to verify the system.Results:The beagle dogs have an obviously regulation on respiratory,cardiovascular system following with the changes of animals' circadian rhythms.Terfenadine could prolong obviously some parameters of ECG,e.g.QTc interphase.Conclusion:Terfenadine,after administrating beagle dogs by the dosage of 30mg/kg,have obviously effect on the QTc parameter and can be acted as a positive compound to apply.Part2QO-58 lysine effect on cardiovascular and respiratory system in conscious dogsObjective: Using implantable telemetry system,to observe the effects of QO-58 lysine on cardiovascular and respiratory system in conscious beagle dogs for a brief evaluation the safety of QO-58 lysine.Methods:Four beagle dogs are administrated by QO-58 lysine compound which divided into three dosage 5,10,20mg/kg,following by a Latin square design,The changes of breath rate,blood pressure,ECG parameters of beagle dogs were recorded with DSI telemetry system and compared the indexes preand post-administration of QO-58lysine1?2?3?4?5?6?7?8?9?10?11?12h using the method of statistical analysis.Results:eagle dogs administrated with QO-58 lysine 5,10,20mg/kg have no statistical difference effects including the breath rate,heart rate and the main ECG parameter(ST-I,QRS,PR,QT,QTcb and QTcf).However,the middle and high dosage have an obvious effect on blood pressure,it is a statistical fall of systolic pressure after administration 10mg/kg QO-58 lysine compound 6~12hours and obviously decrease of diastolic pressure & mean blood pressure after administration 20mg/kg compound 9~12 hours,following with a time and dosage dependence changes rule.Conclusion:QO-58 lysine,as a new chemical compound,has an untoward effect on falling blood pressure above the twice pharmacodynamics dosage,and have no effect on ECG parameters,which has potential functions such as anti-epileptic,anti-convulsions and alleviating peripheralneuropathic pain.