Interaction of midazolam and morphine in the spinal cord of the rat.
The antinociceptive properties, as measured by the tail-flick and hot-plate tests, and the motor effects of an intrathecally-administered benzodiazepine agonist midazolam, alone, and in combination with morphine, was examined in rats. Midazolam alone produced a weak but dose-dependent (20-60 micrograms) antinociceptive effect in addition to a clear motor dysfunction at larger doses (60-100 micrograms). An inactive dose of intrathecally-administered midazolam (20 micrograms) produced a leftward shift in the dose-response curve for intrathecally administered morphine, in the thermal antinociceptive tests. This supra-additive effect was antagonized by naloxone (1 mg/kg). The data suggest a synergistic interaction between mu- and GABAA-receptors in the spinal processing of thermally-evoked pain.
Yanez
A
A
Departamento de Anesthesia, H. Del Insalud A. Marcide, Carretera de Catabois, Ferrol, Spain.
Sabbe
M B
MB
Stevens
C W
CW
Yaksh
T L
TL
D000700:Analgesics; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004576:Electromyography; D005442:Flumazenil / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D008874:Midazolam / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*
D000700:Analgesics; D011963:Receptors, GABA-A; D009270:Naloxone; D005442:Flumazenil; D009020:Morphine; D008874:Midazolam