Ketamine and its isomers have equipotent relaxant effects on tracheal smooth muscle contracted by tachykinins

Abstract

Recent studies indicate that not only inflammatory cells but also neural mechanisms by which tachykinins such as substance P (SP) and neurokinin A (NKA) are released from vagal afferent C-fiber contribute to asthma. Although ketamine (K) has been used in the anesthetic management of asthmatic patients, the mechanism by which K relaxes the airway smooth muscle is still uncertain, and no information exists on any differential effect of K and its isomers. We determined the spasmolytic effect of racemic [R(±)]K and its isomers S(+) K and R(-) K on SP and NKA-induced contraction of tracheal smooth muscle in guinea pigs. Strips of guinea pig trachea were mounted in an organ bath filled with Tyrode's solution at 37°C bubbled with 95% O2/5% CO2. Strip tension was measured isometrically with a force displacement transducer. Strip contraction was elicited with SP 10(-6) M or NKA 5×10(-7) M.R(±), R(-), or S(+) K (4.5-18.0×10(-4)M) was cumulatively administered into the bath. The calculated ED50 values (the concentration that relaxed the contraction by 50%) of R(±), R(-) and S(+) K were 7.6±0.5, 7.8±0.6, and 7.6±0.5 (10(-4)M), respectively, when the contraction was elicited with SP, and 8.0±1.0, 8.2±1.2, and 7.9±1.3 (10(-4)M), respectively, when NKA was used. We concluded that K and its isomers have equipotent spasmolytic effects on airway smooth muscle precontracted with tachykinins.