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Stereospecific effects of ketamine enantiomers on canine tracheal smooth muscle
Author(s) -
Pabelick Christina M,
Rehder Kai,
Jones Keith A,
Shumway Robin,
Lindahl Sten G E,
Warner David O
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701280
Subject(s) - ketamine , enantiomer , chemistry , calcium , contraction (grammar) , muscle contraction , pharmacology , nifedipine , anesthesia , endocrinology , stereochemistry , medicine , organic chemistry
Ketamine is a potent bronchodilator which relaxes airway smooth muscle (ASM). Clinically, ketamine is used as a 1:1 racemic mixture of enantiomers that differ in their analgesic and anaesthetic effects. The aim of this study was to determine whether there was a difference between the enantiomers in their ability to relax isolated ASM and to explore mechanisms responsible for any observed differences. Canine tracheal smooth muscle strips were loaded with fura‐2 and mounted in a photometric system to measure simultaneously force and [Ca 2+ ] i . Calcium influx was estimated by use of a manganese quenching technique. In strips stimulated with 0.1 μ M ACh (EC 50 ) R (−)‐ketamine (1–100 μ M ) caused a significantly greater concentration‐dependent decrease in force ( P <0.0001) and [Ca 2+ ] i than S (+)‐ketamine (1–100 μ M ) ( P <0.0005). In contrast, there was no significant difference between the enantiomers in their ability to inhibit calcium influx (45% decrease in influx rate for R (−)‐ketamine and 44% for S (+)‐ketamine, P =0.782). In strips contracted with 24 m M isotonic KCl (which activates voltage‐operated calcium channels), the enantiomers modestly decreased force and [Ca 2+ ] i ; there was no significant difference between the enantiomers in their effects on force ( P =0.425) or [Ca 2+ ] i ( P =0.604). The R (−)‐enantiomer of ketamine is a more potent relaxant of ACh‐induced ASM contraction than the S(+)‐enantiomer. This difference appears to be caused by differential actions on receptor‐operated calcium channels.