ABSTRACT
Objective To provide the reference resource for the safe clinical use of the compound of diphenhydramine hydrochloride and caffeine by observing its effects on the nervous system, cardiovascular system and respiratory system in experimental animals. Methods Single dose of the compound of diphenhydramine hydrochloride and caffeine was given to animals orally. The effects on climbing ability of mice and blood pressure, electrocardiogram, respiration rate and amplitude in beagle dogs were observed and recorded. Results With the dosage of the compound of diphenhydramine hydrochloride and caffeine (diphenhydramine hydrochloride / caffeine ratio is 1/2.4) at 51, 102, 204 mg/kg, there was no significant effect on the climbing ability in mice. With the dosages of 14.2, 28.3, 56.6 mg/kg for male Beagle dogs and 5.66, 14.2, 28.3 mg/kg for female Beagle dogs, no significant effects were observed in systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, ECG（P wave, R wave , T wave, QRS time, PR interval, QT interval）, respiratory rate and amplitude. Conclusion Under the experimental conditions, single oral dose of the compound of diphenhydramine hydrochloride and caffeine has no significant effect on the nervous system, cardiovascular system and respiratory system in experimental animals. Those results suggest that the compound of diphenhydramine hydrochloride and caffeine is a safe agent for clinical use.
ABSTRACT
Objective To observe the changes of circadian characteristics and stress-response-related physiological parameters including respiration, blood pressure, electrocardiography and body temperature of conscious rhesus monkeys by implantable telemetry technique. Methods Surgery was performed on 8 rhesus monkeys (half male and half female, 3-5 years old) for implantation of a telemetry transmitter. After 3 weeks of recovery, the physiological parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus monkeys without binding were automatically recorded by a DSI telemetry system and the data were analyzed by the Ponemah software. Results Some electrocardiographic indexes showed significant differences at daytime and nighttime (P＜ 0. 05 or P＜ 0. 01) including mean heart rate (HR) ( 155. 0-122. 4 times/min), respiratory rate interval (RR-I) (410. 8-535. 7 ms), T-wave amplitude (T-A) (0. 181-0. 157 mV), PR interval (PR-I) (80. 4-87. 4 ms), QT interval (QT-I) (224. 8-263. 9 ms), and corrected QTcb interval (QTcb) (352. 3-366. 7 ms). The indexes of blood pressure and respiration at daytime were significantly higher than those at nighttime (P＜ 0. 01), including the mean systolic pressure (SYS) at daytime and nighttime (144. 6-131. 6 mmHg), diastolic pressure (DIA) (99. 8- 89. 9 mmHg), mean arterial pressure (MAP) (121. 5-110. 2 mmHg), tidal volume (TV) (64. 5-36. 6 mL), minute ventilation (MV) (1931. 9-920. 1 mL/min), and respiratory rate (RR) (32. 3-25. 4 times/min). Cleaning and feeding activities of the laboratory staff at 9: 00 a.m. and 2: 00 p.m. had a certain effect on the stress-responses in the monkeys. Conclusions The parameters of respiration, blood pressure, electrocardiography and body temperature of the conscious rhesus macaques observed by implanted telemetry system show obvious circadian changes, which can truly reflect the changes of physiological indexes at daytime and nighttime, and avoid the stress in hungry monkeys caused by the feeding and cleaning activities of laboratory staff. This technique can improve the efficiency of drug safety pharmacology studies, reduce the number of animals used and meet the requirements of 3R principles.
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Objective To study the effects of Dexibuprofen injection on the central nervous,cardiovascular and respiratory systems in animals.Methods The effect of Dexibuprofen injection on central nervous system was observed by autonomic activities experiment,mice concordant ability experiment and hypnotize experiment induced by pentobarbital.The effects of Dexibuprofen injection on circulatory system and respiratory system were observed by measuring the implanted telemetry system,blood pressure,ECG;respiratory rate and tidal volume of Beagle's dogs.Results Dexibuprofen injection (80 mg/kg) showed synergistic action with pentobarbital,and no significant effects on autonomic activities and concordant ability at doses of 20,40 and 80 mg/kg in mice.Dexibuprofen injection at doses of 10,20 and 40 mg/kg had no effect on the central nervous,cardiovascular and respiratory systems.In the same dose,the adverse reaction of Dexibuprofen injection was not increased compared with Ibuprofen injection.Conclusion Dexibuprofen injection (mice 40 mg/kg,dog 40 mg/kg) has none toxicity on cardiovascular,respiratory and central nervous systems,but at the dose of 80 mg/kg in mice has obvious effect on central nervous system.
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Objective To prove the advantages of telemetry by comparing with the traditional methods in safety pharmacology.Methods To monitor continuously the heart rate, respiratory rate, blood pressure and ECG of Beagle dogs by traditional and telemetry methods respectively, analyze and compare the changes between anesthetized and conscious dogs before and after feeding.Results Maintenance of anesthesia changed significantly the heart rate, respiratory rate, blood pressure and QT interval in the ECG of animals.The changes of physiological indicators in 24 h is not obvious in conscious animals, and showed a certain biorhythm.Compared with the conscious animals, the anesthetized dogs’ heart rate was significantly higher, blood pressure increased significantly, QRS and QTcf interval prolonged significantly, respiratory frequency decreased, heart rate increased significantly after feeding, and QTcf interval extended very significantly.Conclusions Traditional methods in safety pharmacology affect animal physiological indicators such as heart rate, blood pressure, respiratory rate and QT interval, which affect the objectivity of drug evaluation.Using conscious animals by telemetry can reduce these errors, however, the interference from outside should be eliminated.
ABSTRACT
Spontaneous locomotor activity is a widely used evaluation method in safety pharmacology of central nerve system and investigation of neuroscience.Spontaneous locomotor activity test is an important method that can investigate several animals' species and their associated indexes of spontaneous locomotor activity;it can also provide parameters for several pharmacological objectives including safety pharmacology of central nerve system.The new developed equipments and methods have many merits.This paper reviews the progress of methodology of spontaneous locomotor activity test in rats,pigs and monkeys.