PMID: 8445997Jan 1, 1993Paper

Does midazolam inhibit the development of acute tolerance to the analgesic effect of alfentanil?

Life Sciences
I KissinE L Bradley

Abstract

Alfentanil-midazolam analgesic interactions were studied in rats with continuous infusions or bolus injections of the drugs. Analgesia was determined by measuring the threshold of motor response to noxious pressure. The continuous constant-rate infusion of alfentanil demonstrated that after an initial peak, the analgesia profoundly declined due to the development of acute tolerance. When alfentanil (250 micrograms.kg-1.h-1) was given together with midazolam (3 mg.kg-1.h-1), the decline in the analgesic effect of alfentanil was attenuated. Following the 4 h period of the constant-rate (250 micrograms.kg-1.h-1) infusion of alfentanil, when acute tolerance was already developed, midazolam (3 mg.kg-1) given as a bolus injection enhanced the alfentanil-induced anesthesia. At the same time, when alfentanil was given as a bolus injection (30 micrograms.kg-1) with or without midazolam (3 mg.kg-1) also by bolus injection, no changes were seen to indicate an enhancement of the analgesic effect of alfentanil by midazolam. The results suggest that midazolam attenuates the development of acute tolerance to the analgesic effect of alfentanil.

References

Nov 11, 1991·Anesthesiology·I KissinE L Bradley
Apr 1, 1990·Neuropharmacology·A YanezT L Yaksh
May 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·M MiyakeR A North
Nov 4, 1988·Science·G F Koob, F E Bloom
Feb 1, 1986·Pharmacology, Biochemistry, and Behavior·F V Abbott, K B Franklin
Jun 1, 1965·Proceedings of the Society for Experimental Biology and Medicine·M COHENG UNGAR

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Citations

May 10, 1996·Neuroscience Letters·J P ZacnyJ L Apfelbaum
Apr 12, 2007·International Anesthesiology Clinics·Mark L Baccei

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