Effects of bupivacaine and its isomers on guinea pig tracheal smooth muscle.
The effects of racemic bupivacaine and its (-)-(S)- and (+)-(R)-isomers on guinea pig tracheal smooth muscle tension were studied in vitro. Racemic bupivacaine had a dual action with contraction at low concentrations (6.9-55 x 10(-6) M) and relaxation at high concentrations (1.1-18 x 10(-4) M), (-)-(S)-Bupivacaine had dual action comparable to that of racemic bupivacaine, while (+)-(R)-bupivacaine had only weak contractile effects with more marked relaxant effects. The contractile effects of bupivacaine were abolished in Ca(2+)-free medium and by verapamil, while the relaxant effects were not influenced by verapamil or Ca(2+)-free medium. The (-)-(S)-isomer is responsible for the contractile effects of racemic bupivacaine, whereas both (-)-(S)- and (+)-(R)-isomers contribute to its relaxant effects. In preparations denuded of epithelium, the (maximal) responses were attenuated to 86% of maximum contraction and 48% of maximum relaxation, suggesting that the epithelium plays a larger role in relaxant than in contractile responses to bupivacaine. It is concluded that bupivacaine has a dual action on guinea pig tracheal smooth muscle with epithelium-independent. Ca(2+)-dependent contraction at low concentrations and epithelium-dependent, Ca(2+)-independent relaxation at higher concentrations.
Lee
T L
TL
Department of Anaesthesia, National University of Singapore.
Adaikan
P G
PG
Lau
L C
LC
Ratnam
S S
SS
Dambisya
Y M
YM
D000818:Animals; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects*
D002045:Bupivacaine