Use of within-group designs to test anti-tussive drugs in conscious guinea-pigs

作者: R. Venkatasamy , A. McKenzie , C.P. Page , M.J. Walker , D. Spina

DOI: 10.1016/J.VASCN.2010.02.015

关键词: DrugDrug deliveryDrug developmentPositive pressureExpirationCough reflexAnesthesiaConcentration dependenceDrug actionPharmacologyMedicine

摘要: Abstract Introduction Cough is a common medical problem for which there are few effective drug treatments. A limited understanding of the mechanisms induction and maintenance cough paucity suitable animal models frustrate discovery efforts to find novel anti-tussives. As in humans, guinea-pigs evoke reflex upon exposure tussive agents such as citric acid capsaicin; both have been widely used assess anti-tussive drugs. However, potential using within-group designs development has received little attention may offer way assisting effort area well other areas. Methods can be monitored conscious by placing animals Perspex chamber, air continually exchanged use negative pressure delivery aerosols chamber accurately timed. response agent (e.g. 0.2–0.4 M acid; 10–30 μM capsaicin) detected simultaneous microphonic recording audible signals characteristic positive changes generated dependent rapid expiration from lungs. Both sound recorded an online analyzer, whilst number coughs analyzed off-line. The over 15 min period quantitate events. Results Reproducible cross-over that lend themselves studies. time concentration dependence action evaluated same animal. Furthermore, effect different drugs thereby reducing between group error improving sensitivity test. Discussion Repeated measures design improves precision with evaluate preclinical could make process more efficient.

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