GABA alpha6 receptors mediate midazolam-induced anxiolysis.
OBJECTIVE
To compare the ability of midazolam to produce sedation and anxiolysis and attenuate memory in 100 patients aged 20 to 70 years. The effect of a point mutation (Pro385Ser) for the gamma amino-butyric acid (GABA) alpha6 receptor on the sedative, anxiolytic, and memory effects of midazolam was determined.


METHODS
University hospital.


METHODS
Prospective, randomized, double-blind study.


METHODS
100 ASA physical status I and II patients scheduled for surgery.


METHODS
Two midazolam dose groups, 20 microg/kg and 40 microg/kg, with 40 patients per group and 20 control patients receiving saline as a sham control. Treatments were randomly assigned. Blood was collected at the beginning of each study.


METHODS
Patient sedation and anxiolysis were measured using a visual analog scale and explicit and implicit memory of a word task determined before and six minutes after midazolam or saline. A 365-base pair fragment of the GABA alpha6 receptor gene was amplified by polymerase chain reaction (PCR) from patient blood DNA and digested with the restrictase Fok I. Restriction fragments were visualized by ethidium bromide staining after electrophoresis to evaluate the GABA alpha6 receptor subunit mutation.


RESULTS
Midazolam produced dose-related sedation and anxiolysis. Explicit (recall) memory was attenuated with high-dose midazolam but implicit (recognition) memory remained intact. The GABA alpha6 receptor mutation did not affect baseline sedation, anxiety, or memory but significantly attenuated the anxiolytic effect of low-dose midazolam. Sedation and explicit memory were not affected by the mutation.


CONCLUSIONS
A Pro385Ser mutation of the GABA alpha6 receptor subunit decreased the anxiolytic effect of low-dose midazolam.
Hoffman
William E
WE
Department of Anesthesiology, University of Illinois at Chicago, 60612, USA. whoffman@uic.edu
Balyasnikova
Irina V
IV
Mahay
Harkinder
H
Danilov
Sergei M
SM
Baughman
Verna L
VL
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D001008:Anxiety Disorders / Q000139:chemically induced*; D004311:Double-Blind Method; D005260:Female; D006785:Hospitals, University; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D008874:Midazolam / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D011446:Prospective Studies; D011963:Receptors, GABA-A / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D008874:Midazolam