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British Journal of Anaesthesia, Vol 77, Issue 3 375-380, Copyright © 1996 by The Board of Management and Trustees of the British Journal of Anaesthesia

LABORATORY INVESTIGATIONS

Synergistic interactions between midazolam and alfentanil in isolated neonatal rat spinal cord

J. Feng and J. J. Kendig
Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305-5117, USA

Benzodiazepines, which may themselves have analgesic properties, display complex interactions with opioids. This study was designed to investigate the effects of midazolam on nociceptive neurotransmission in isolated neonatal rat spinal cord, and the interactions between midazolam and alfentanil. Slow ventral root potentials (sVRP) were recorded from a lumbar root of spinal cords isolated from 1-7-day-old rats and superfused at 27-28 degrees C. Midazolam (35 nmol litre-1 to 15 microgramsmol litre-1) significantly (P < 0.05) depressed sVRP area in a concentration-dependent manner. Midazolam depression was antagonized by flumazenil, bicuculline and naloxone. Midazolam and alfentanil interacted synergistically, as determined by a combination index of less than 1. Midazolam blocked the rebound hyperexcitability observed when alfentanil was reversed by naloxone. The results of the study are relevant to benzodiazepine-opioid analgesia and to the effectiveness of benzodiazepines in mitigating the development of opioid tolerance and dependence.
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J. J. Kendig
In vitro networks: subcortical mechanisms of anaesthetic action
Br. J. Anaesth., July 1, 2002; 89(1): 91 - 101.
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