Antinociceptive Interaction Between Opioids and MedetomidineSystemic Additivity and Spinal Synergy
作者:
Michael Ossipov,
Sarah Harris,
Patricia Lloyd,
Elina Messineo,
B. Lin,
Jerome Bagley,
期刊:
Anesthesiology
(OVID Available online 1990)
卷期:
Volume 73,
issue 6
页码: 1227-1235
ISSN:0003-3022
年代: 1990
出版商: OVID
关键词: Analgesics, opioid: fentanyl; meperidine; morphine;Drug interactions: isobolographic analysis;Sympathetic nervous system, alpha-2 agonists: medetomidine
数据来源: OVID
摘要:
The antinociceptive interaction on the tail flick (TF) and hot plate (HP) tests between opioid analgesics and medetomidine after intravenous (iv) or intrathecal administration were examined by isobolographic analysis. Male Sprague-Dawley rats received fixed ratios of medetomidine to morphine, fentanyl, and meperidine of 1:10 and 1:30, 10:1, and 1:3, respectively, by iv administration or 10:1 3:1 and 10:1, and 1:3 by intrathecal administration, respectively. Data were expressed as the percentage maximal possible effect (%MPE). The A50(dose producing 50% MPE) for each drug or drug combination was determined from the dose-response curve. Isobolographic analysis revealed that the effect of medetomidine combined with fentanyl, morphine, or meperidine was additive after iv administration. The intrathecal administration of combinations of medetomidine with the opioids produced a synergistic antinociceptive effect in the TF but not HP test. These data confirmed that the interaction between medetomidine and opioids in producing antinociception may be additive or synergistic, depending on the route of administration, drug ratio administered, and level of processing of the nociceptive input (i.e., spinalvs.supraspinal). Moreover, these results were consistent with a spinal role for alpha-2 adrenoceptors in mediating antinociception. The authors suggest that the interaction between the opioid and alpha-2 adrenergic receptors occurs within the spinal cord.
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