GABA α6 receptors mediate midazolam-induced anxiolysis

William E. Hoffman*, Irina V. Balyasnikova, Harkinder Mahay, Sergei M. Danilov, Verna L. Baughman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Study 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) α6 receptor on the sedative, anxiolytic, and memory effects of midazolam was determined. Setting: University hospital. Design: Prospective, randomized, double-blind study. Patients: 100 ASA physical status I and II patients scheduled for surgery. Interventions: Two midazolam dose groups, 20 μg/kg and 40 μg/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. Measurements: 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 α6 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 α6 receptor subunit mutation. Main 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 α6 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 α6 receptor subunit decreased the anxiolytic effect of low-dose midazolam.

Original languageEnglish (US)
Pages (from-to)206-209
Number of pages4
JournalJournal of Clinical Anesthesia
Volume14
Issue number3
DOIs
StatePublished - Jun 5 2002

Keywords

  • Age factors
  • GABA receptors
  • Gamma aminobutyric acid
  • Genetics
  • Midazolam

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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